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New Concepts in Cancer Biomarkers: Circulating miRNAs in Liquid Biopsies

Erika Larrea, Carla Sole, Lorea Manterola and 8 more

International Journal of Molecular Sciences · 2016 · Review · CC BY

doi:10.3390/ijms17050627

Abstract

The effective and efficient management of cancer patients relies upon early diagnosis and/or the monitoring of treatment, something that is often difficult to achieve using standard tissue biopsy techniques. Biological fluids such as blood hold great possibilities as a source of non-invasive cancer biomarkers that can act as surrogate markers to biopsy-based sampling. The non-invasive nature of these “liquid biopsies” ultimately means that cancer detection may be earlier and that the ability to monitor disease progression and/or treatment response represents a paradigm shift in the treatment of cancer patients. Below, we review one of the most promising classes of circulating cancer biomarkers: microRNAs (miRNAs). In particular, we will consider their history, the controversy surrounding their origin and biology, and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 21, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Cancer represents the leading cause of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer related deaths in 2012, and this number is predicted to rise by approximately 70% over the next two decades according to the World Health Organization. The effective and efficient management of cancer patients relies upon both early diagnosis and the frequent monitoring of patient response to treatment.

The current gold standard of cancer diagnosis is the histological examination of tissue, obtained either by radiologically guided biopsy or surgical excision. However, these procedures are invasive, expensive, and not without risk to the patient. They also take time and need to be consistently evaluated by expert pathologists. Therefore, there is a clear clinical need for alternative diagnostic techniques. In particular, the use of biological fluids such as blood as a source of non-invasive biomarkers of cancer has raised a great deal of interest. So-called “liquidbiopsies” hold great clinical promise, as their non-invasive nature allows for rapid, economical, and repeat sampling—features that permit their use in screening programs and for the close monitoring of treatment response and disease progression, allowing for earlier intervention and dynamic treatment management. Furthermore, there is an increasing awareness of the genetic heterogeneity of tumors and a realization that tissue biopsies may miss this diversity. Liquid biopsies in contrast can capture the entire genetic panorama of the tumoral landscape. Consequently, this technology has the potential to radically improve current treatment regimens and therefore the outcome of cancer patients, allowing for a personalized approach to be taken for each patient. Although the majority of liquid biopsy research to date has focused upon the isolation of circulating tumor cells (CTCs), these cells are relatively rare and require sensitive collection and enrichment technology. Increasingly, the focus of liquid biopsy studies is shifting towards circulating (or cell-free) nucleic acids (cfDNA/RNA) as being easier to collect and analyze. There has been a particular interest in circulating cell-free microRNAs (cfmiRNAs), the subject of this review. For a wider overview of circulating nucleic acids as cancer biomarkers—in particular, mRNA and non-coding RNAs other than microRNAs (miRNAs)—we refer the reader to our previous article.

The history of circulating (blood) nucleic acids goes back to a finding in 1947 by Mandel and Metais of RNA and DNA in the plasma of healthy and sick individuals. Remarkably, this report predates the realization that DNA was the molecule responsible for inheritance and the discovery of the double helix structure by Watson and Crick. It was not until the 1960s when scientific interest was aroused by the finding of cfDNA in patients with the autoimmune diseases, systemic lupus erythematosus (SLE) and rheumatoid arthritis. However, it was not until 1977 when the potential of cfDNA as cancer biomarkers was postulated—when Leon et al. reported elevated levels of circulating cfDNA in pancreatic cancer patients. After that, in 1994, cancer-specific DNA mutations in NRAS (myelodysplastic syndrome (MDS)) and KRAS (pancreatic cancer) were found in the blood of cancer patients. cfRNA, in contrast to cfDNA, was not identified until 1999, when Lo et al. first identified (viral) cfRNA in the blood of nasopharyngeal carcinoma patients. Several years later, in 2007, our group reported the presence of miRNAs in the blood of lymphoma patients; the following year, it was demonstrated that miRNAs could be useful as non-invasive biomarkers of cancer.

miRNAs are endogenous, small (18–24 nt), non-coding (nc) RNA molecules that regulate eukaryotic gene expression post-transcriptionally. miRNAs were unknown in science until just over 20 years ago, and, even then, were not formally recognized until 2001. There are now over 2500 human miRNAs that have been identified, and it is believed that nearly two thirds of all human genes are directly targeted by miRNAs. miRNAs have been shown to play key regulatory roles in virtually every aspect of biology, including in the pathogenesis of cancer, and are aberrantly expressed in many diseases (Figure 1). Indeed, there is now compelling evidence that miRNAs regulate all aspects of the so-called “hallmarks of cancer” that enable tumor growth and metastatic dissemination (Figure 2).

The field of circulating miRNAs has generated a great deal of interest and has been growing at an exponential rate with more than 2000 publications now published on the subject (source: PubMed; Figure 1), and many conferences and commercial entities are involved in this area. Below, we discuss some of the controversies behind the origin of these molecules and their possible functions. We also review some of the major evidence to suggest their potential as cancer biomarkers, but, most importantly, we discuss some the barriers that are still to be overcome if these molecules are to become a part of routine clinical practice.

1.1. Origin of Extracellular miRNAs

There are several different hypotheses that have been proposed to explain the presence of circulating miRNAs in biological fluids. These include the passive release of miRNAs from broken cells after tissue injury, cell apoptosis or necrosis, chronic inflammation, and from cells with a short half-life such as platelets. For example, specific miRNAs are elevated in blood after myocardial infarction or hepatobiliar injury. An alternative hypothesis, though not mutually exclusive, is that miRNAs are actively secreted from cells either shuttled via microvesicles such as exosomes or shedding vesicles, or directly in complex with RNA-binding proteins or lipoproteins such as nucleophosmin (NPM1), high-density lipoprotein (HDL), or Argonaute proteins.

There is some controversy as to which of these represent the true origin of cfmiRNA, or at least the relative proportion of the different routes; until fairly recently, it was believed that most circulating miRNAs were derived from cell-derived vesicles.This has been contested by at least two independent reports that suggest that more than 90% of the miRNAs in blood are membrane-free and associated with Ago proteins. Irrespective of their origin, the composition of cfmiRNAs appears to differ greatly from their respective donor cells. In fact, some secreted miRNAs are notpresent at all in the parental cells.

1.2. Cell–Cell Communication (Hormone-Like Molecules)

Aside from their (passive) role as biomarkers, there has been a great deal of interest in the function of cfmiRNAs and in particular their ability to act as signaling molecules that potentially allow tumor cells to modify the bodies response to its own advantage. The first evidence that extracellular miRNAs could act as signaling molecules was discovered in plants in 1996. There is now emerging evidence of human miRNAs acting in a similar fashion either as paracrine signalers or even as systemic communicators between cells in an endocrine manner (in a hormone-like way). A number of facts support this possibility: miRNAs appear to be selectively packaged and secreted; extracellular miRNAs are protected from RNases either by lipoprotein or protein carriers or by microvesicle membranes; and circulating miRNAs are able to alter gene expression in recipient cells and mediate functional changes in them. The first indication that miRNAs could shuttle between cells via exosomes was demonstrated in mast cells. Later, the transfer of miRNAS between different cell types (embryonic stem cells and fibroblasts) was demonstrated. More recently, exosomal miRNA has been shown to be able to modulate inmunological response through modification of the gene expression of antigen presenting cells (APC) by T-cells, B-cells, and dendritic cell-derived miRNAs.

Multiple studies suggest that cfmiRNAs could play a role in cancer biology through tumor-derived exosomal miRNA modulating non-tumor cells to the ultimate benefit of the tumor. For example, exosomal-cfmiRNAs have been demonstrated to modulate chemosensitivity, angiogenesis, and cell invasiveness. While this is potentially a fascinating phenomena, this is still a contentious issue, and it is worth remembering that the few studies carried out to date have been almost exclusively in vitro. Finally, although Ago2-boundmiRNAs appear to form the majority of cfmiRNA, there is no evidence (or known mechanism) for the active release of vesicle-free AGO2-miRNA complexes in mammals, nor any indication of Ago-2 surface receptors for the uptake by recipient cells. Therefore, the physiological relevance of cfmiRNA as an intercellular signaling mechanism remains to be determined.

2. miRNAs as Cancer Biomarkers

According to the National Cancer Institute, a biomarker is defined as “a biological molecule found in blood, other body fluids, or tissues that are a sign of a normal or abnormal process, or of a condition or disease.” In cancer, they can be divided into three general categories: (1) diagnostic biomarkers, which are used for a differential diagnosis; (2) prognostic biomarkers, which can distinguish tumors with a good outcome from those with a bad outcome; and (3) predictive biomarkers, which are for assessing whether a treatment is likely to be effective for a particular patient or not. An ideal biomarker should have a high specificity, sensitivity, and predictive power. miRNAs have a number of intrinsic characteristics that make them attractive as biomarkers. Firstly, they are highly specific, and it has been shown that miRNA expression profiles differ between cancer types according to diagnosis and the developmental stage of the tumor, with a greater resolution than traditional gene expression analysis. Secondly, unlike other RNA classes, miRNAs are remarkably stable and therefore can be robustly measured not only in biological fluids but also from routinely prepared formalin-fixed paraffin-embedded (FFPE) material. Indeed, unlike other RNA species, miRNAs appear resistant to boiling, pH changes, repeated freeze-thawing cycles, and fragmentation by chemical or enzymes. It should be noted, however, that cfmiRNAs are not themselves intrinsically resilient to RNase or any other treatment; rather, they are protected by their lipidic or protein-based carrier. As a result of these characteristics, the use of cfmiRNAs as biomarkers—and in particular as cancer biomarkers—has generated a plethora of publications over the last few years. Due to the limitations of space, we will not attempt to review all of these but instead discuss the more robust studies that identify common cfmiRNA biomarkers in multiple studies. More often than not, these biomarker miRNAs are themselves intimately involved in cancer pathology, as shown in Table 1, which includes their respective experimentally validated targets. While it may be tempting to speculate that these miRNAs may have the same effect while in circulation as intracellularly, there is no evidence that this is indeed the case.

2.1. let-7 Family (let-7a, -7b, -7c, -7e, -7f, -7i)

There are 13 different let-7 family members in humans: let-7a-1, 7a-2, 7a-3, 7b, 7c, 7d, 7e, 7f-1, 7f-2, 7g, 7i, miR-98, and miR-202. Differential expression of let-7 family members has been described to be downregulated in a wide variety of cancers such as melanoma, pancreatic cancer, prostate cancer, and sarcoma, although some, including lymphoma, mesothelioma, and breast cancer, have been shown to be upregulated; thus, the let-7 family is generally regarded as a tumor suppressor. let-7 has been shown to be a direct regulator of some important oncogenes, such as the three RAS genes, HMGA2, STAT3, UHRF2, and MYC; additionally, let-7 family targets cell cycle and cell proliferation genes; finally, apoptosis is also shown to be regulated by let-7 family, through CASP3 targeting. RNase III nuclease, known to process pre-miRs, was also confirmed as a direct target of the let-7 family, so they might regulate their own processing.

let-7 family members have been identified differentially expressed and therefore have been proposed as diagnostic tools in serum/plasma of many cancer types including lung cancer (let-7a, let-7c, let-7f), prostate cancer (let-7a), gastric cancer (let-7a, let-7c, let-7i, let-7f), ovarian cancer (let-7b, let-7f, let-7i), hepatocellular carcinoma (HCC) (let-7b, let-7f), breast cancer (let-7c, let-7b, let-7g), acute myeloid leukemia (AML) (let-7b, let-7d), thyroid carcinoma (let-7e), and colorectal cancer (CRC) (let-7a). Recently, let-7f has also been detected as deregulated in the feces of CRC patients. However, their potential as prognostic biomarkers has also been highlighted in several cancer types such as myelodisplasia (let-7a), lung cancer (let-7b, let-7f, let-7i), hepatocellular carcinoma (let-7b, let-7f), multiple myeloma (let-7e), prostate cancer (let-7d), ovarian cancer (let-7f), and breast cancer (miR-202). In general, low let-7 levels are associated with poor prognosis including overall survival, early recurrence, and tumor size.

2.2. miR-10b

miR-10b acts as a metastasis driver in many different types of cancers such as breast cancer, glioma, and oesophageal cancer, among others, specifically promoting cell mobility and invasiveness. Validated targets of this miRNA include SDC1, HOXD10, KLF4, MICB, and CDH1. It also regulates E2F1-mediated transcription through p21/CDKN1A regulation and important cell cycle regulators such as BUB1, PLK1, and CCNA2.

Circulating miR-10b levels have been described as being upregulated in patients with ovarian cancer, lung cancer, oesophageal, and glioblastoma compared to healthy controls. Consistent with this, miR-10b is increased in plasma from metastatic breast cancer patients and in the cerebrospinal fluid of patients with brain metastasis of both breast and lung cancer.

2.3. miR-16

miR-16 has an important role in regulating apoptosis in different cancer types including lung, breast, liver, glioblastoma, and squamous cell carcinoma through targeting FEAT/METTL13, RPS6KB1, IGF1R, CCND1, BCL2, RECK, and/or SOX6. This miRNA is also an important regulator of cell cycle molecules including FG2F, CCNE1, and E2F1, as well as cell autophagy (mTORC2) and metastasis (SOX5).

Circulating miR-16 has been described significantly differentially expressed in patients compared with healthy controls in several cancers: oral cancer, breast cancer, prostate cancer, osteosarcoma, gastric cancer, liver carcinoma, and oesophageal carcinoma. Furthermore, miR-16 is also associated with prognosis and tumor size in gastric cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma (ESCC).

2.4. The miR-17~92 Cluster

Over-expression of the miR-17~92 cluster is a key oncogenic event in many cancer types, and overexpression in murine models result in tumor formation. This cluster is composed of different miRNAs: miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-92, and miR-106a/b with a variety of related functions, primarily targeting tumor suppressor molecules and pathways such as PTEN and RB1, and molecules in the TGFβ signaling pathway such as TGFBR2, SMAD2, and SMAD4. These miRNAs also target senescence (p21/CDKN1A), metastasis (DLC1 and TIMP2), cell cycle regulation (E2F family members, RB1 and p21/CDKN1A), and angiogenesis (THBS1 and CTGF).

Circulating members of the miR-17~92 cluster have been widely described as being deregulated in many cancer types including colorectal cancer, gastric cancer, squamous cell carcinoma, breast cancer, bladder cancer, hematological malignancies, lung cancer, prostate cancer, osteosarcoma, oesophageal carcinoma, ovarian cancer, and hepatocellular carcinoma. They have also been shown to have prognostic value in colorectal cancer, sporadic melanoma, breast cancer, bladder cancer, multiple mieloma, lung cancer, and prostate cancer. Moreover, levels of circulating miR-17~92 miRNAs have been associated with the response to chemotherapy (i.e., predictive biomarkers) in both breast cancer and multiple myeloma.

2.5. miR-21

miR-21 acts mainly as an oncogene (“onco-miR”) because most of its target genes are tumor suppressors. The list of these target genes is extensive, and they are related to all hallmarks of cancer. One of the principal miR-21 targets is PDCD4, which is a tumor suppressor gene that inhibits PMA-induced neoplastic transformation, tumor promotion and progression, and invasion and intravasation. miR-21 targets multiple components of TP53, TGFB1, and mitochondrial apoptosis tumor suppressive pathways (including HNRPK and TP63). Other targets of miR-21 have been related mainly with apoptosis, cell growth, migration, and invasion, such as BCL2, PTEN, RECK, RHOB, and TPM1, among others.

Circulating miR-21 has been described in a lot of different cancers as a diagnostic, predictive, and/or prognosis biomarker. Some of these are hematological cancers, breast cancer, gastric cancer, ovarian cancer, pancreatic cancer, colorectal cancer, lung cancer, and liver cancer, among others.

2.6. The miR-29 Family (miR-29a, -29b, and -29c)

The miR-29 family members act as tumor suppressors, and their downregulation is associated with many cancer types including leukemia, melanoma, liver cancer, colon cancer, cervical cancer, lung cancer, and prostate cancer. In many studies, downregulation of miR-29 has correlated with more aggressive forms of cancer and shorter overall survival. It has been demonstrated to directly target genes involved in the control of the cell cycle (CDK6) and apoptosis (MCL1, BCL2 and FHIT), as well as genes that promote cell migration and invasion (LAMC1, CDC42). Furthermore, the miR-29 family target genes such as PIK3R1 and CDC42 that normally suppress TP53.

Differential expression of miR-29 family members in plasma/serum has been observed in several cancer types. The expression levels of all the miR-29 family members were upregulated in sera of patients with osteosarcoma. In particular, miR-29a and miR-29b were associated with poor prognosis. miR-29a has been shown to be upregulated in colorectal cancer and therefore has been proposed as a potential non-invasive biomarker for early detection of colorectal cancer, also involving liver metastasis. It has also been found to be upregulated in breast cancer and downregulated in oral and ovarian cancer, compared with healthy controls. Similarly, serum levels of miR-29b have been proposed as potential biomarkers for diagnosis and prognosis of colorectal cancer, whereas miR-29c could be useful as a predictor of postoperative early relapse. However, it was found to be downregulated in serum of nasopharyngeal carcinoma patients, compared with controls.

2.7. The miR-30 Family (miR-30a, -30b, -30c, -30d, and -30e)

Similar to the miR-29 family, miR-30 family members appear to act primarily as tumor suppressors in several cancer types such as ovarian cancer, breast cancer, non-small cell lung cancer (NSCLC), and colorectal carcinoma, although they have also been reported as oncogenes. Several genes have been described to be regulated by the miR-30 family, such as some epithelial-to-mesenchymal transition (EMT)-associated genes, anti-apoptotic protein AVEN, and DLL4 which has a fundamental role in angiogenesis.

Members of the miR-30 family have been identified differentially regulated in body fluids, but their potential as biomarkers has mostly been reported in combinations with other miRNAs. For example, a blood test based upon a combination of the levels of five miRNAs including miR-30c has been described to effectively differentiate prostate cancer patients from benign prostatic hyperplasia (BPH) patients and healthy controls. In addition, the combination of four plasma circulating miRNAs, including miR-30c and serum PSA, has a greater potential to be used as a noninvasive diagnostic biomarker for prostate cancer screening than PSA testing alone. Similar studies have been reported for miR-30c and miR-30a-3p in lung adenocarcinoma, miR-30a in esophageal adenocarcinoma, and miR-30d in lung cancer. In hepatocellular carcinoma, miR-30e has been recently found to be downregulated in serum when compared with healthy controls, and, in lung cancer, high levels of miR-30d in serum have been associated with a shorter overall survival.

2.8. The miR-34 Family (miR-34a, -34b, and -34c)

Members of the miR-34 family are well known to regulate cell cycle, senescence, apoptosis, and invasiveness in cancer, and deregulation of miR-34a has been reported in several types of cancers. The miR-34 family targets multiple TP53 inhibitor genes (MDM4, SIRT1, MTA2, HDAC1, and YY1) and promotes proliferation arrest and induction of apoptosis by targeting MYC, CDK6, and MET. These genes encode factors required for G1/S transition (MYC, E2F, CDK4, and CDK6), anti-apoptotic proteins (BCL2, SIRT1), and proteins involved in invasion (MET). It has also been reported to target pluripotency genes such as NANOG, SOX2, and MYCN and components of Wnt signaling pathways and notch signaling pathways, which regulate growth, epithelial–mesenchymal transition (EMT), and metastasis.

Elevated levels of miR-34a in serum can discriminate between breast cancer patients and healthy controls, and are also associated with the presence of overt metastasis. High levels of circulating miR-34a have also been observed in ovarian and lung cancer, and miR-34b has been found to be upregulated in serum from prostate cancer patients. In osteosarcoma patients, miR-34b levels were found to be downregulated when compared with controls, and these expression levels were significantly decreased in the metastatic patients. Similarly, downregulation of circulating miR-34c in serum of NSCLC patients and miR-34b/c in serum of breast cancer patients has been reported and might have potential as biomarkers for the diagnosis of these pathologies.

2.9. The miR-125 Family (miR-125a and -125b)

miR-125 has been shown to act as a tumor-suppressor in several cancers including ovarian cancer, bladder cancer, breast cancer, hepatocellular carcinoma, melanoma, cutaneous squamous cell carcinoma, and osteosarcoma. miR-125 targets several genes associated with carcinogenesis such as transcription factors (STAT3 and E2F3), matrix-metalloprotease (MMP11 and MMP13), members of the BCL2 family, and growth factors (VEGFA).

Deregulated levels of miR-125a were present in the saliva of oral squamous cell carcinoma (OSCC) patients and in serum of NSCLC patients compared with healthy controls. In a similar way, miR-125b levels were significantly lower in glioma patients and in serum-derived exosomes of melanoma patients. In addition, low circulating levels of miR-125a have been associated with poor prognosis in both breast cancer and hepatocellular carcinoma. In contrast, miR-125b was found to be upregulated in the plasma and serum of metastatic prostate cancer patients, breast cancer, OSCC, colorectal cancer, and NSCLC, in comparison with healthy controls, and to be associated with poor prognostic outcome and chemotherapeutic resistance in this cancer.

2.10. miR-155

miR-155 is involved in both physiological (hematopoiesis andimmune response) and pathological processes. The oncogenic role of miR-155 is well established in both hematological malignances as well as solid cancers such as breast cancer, where its overexpression is generally correlated with poor prognosis. Validated miR-155 target genes are present in multiple pathways associated with cancer and cancer progression, including EMT (SMAD5), proliferation (SOCS1, INPP5D, and CSF1R), block of differentiation (SPI1, CEBPB), and apoptosis (CASP3, FADD, APAF1, and FOXO3A).

In many studies, differentially expressed levels of circulating miR-155 have been identified, including breast cancer, colorectal cancer, lung cancer, AML, diffuse large B-cell lymphoma (DLBCL), and esophageal cancer, making it a potential non-invasive diagnostic biomarker for early detections in these pathologies. In fact, a biosensor for miR-155 detection in plasma has recently been developed for the diagnosis of breast cancer. Elevated levels of miR-155 are also related to overt metastasis in breast cancer, and these high levels have also been identified not only in blood but also in the urine of breast cancer patients. In addition, miR-155 has been also suggested as a prognostic biomarker in chronic lymphocytic leukemia (CLL) and adult T-cell leukemia (ATL), and as a predictive biomarker to response to therapy in CLL.

2.11. The miR-200 Family (miR-200a, -200b, -200c, -141, and -429)

The miR-200 family is believed to play crucial roles in both cancer initiation and metastasis—in particular, in epithelial-mesenchymal transition (EMT)—primarily through the targeting of ZEB1 and ZEB2 transcription factors. It has also been associated with angiogenesis by the targeting of VEGFA and VEGF receptors and pro-angiogenic ligands such as CXCL8 and CXCL1.

Elevated serum levels of miR-200a, miR-200b, miR-200c, and miR-141 have been suggested as good biomarkers for diagnosis and prognosis in ovarian cancer, and serum levels of miR-429 were associated with poor overall survival in NSCLC. In addition, elevated levels of circulating miR-141 have been identified to show diagnostic potential in patients with upper urinary tract urothelial cancer, lung cancer, prostate cancer, breast cancer, and bladder cancer. In breast and bladder cancer, this upregulation is also associated with prognosis. Furthermore, miR-200c was found significantly elevated in the plasma of patients with colorectal cancer, gastric cancer, and breast cancer, and this upregulation was associated with poor prognosis. In colorectal cancer, it has also been identified as a metastasis predictive biomarker as well as miR-141. Similarly, miR-200c can be useful to predict prognosis in NSCLC and in esophageal cancer. In the latest research, the serum level of miR-200c, as well as miR-200b, can be useful for predicting response to chemotherapy, and also has prognostic value in prostate cancer and predictive value in docetaxel chemotherapy outcomes.

2.12. miR-210

miR-210 is strongly linked with the hypoxic pathway and angiogenesis through the targeting of EFNA3, VEGF, and STAT3. miR-210 also acts upon cell cycle and apoptotic pathways by targeting E2F3, MNT, FGFRL1, BCL2, and STAT3. Furthermore, miR-210 can inhibit DNA damage repair genes such as RAD52 and oncogenes such as HOXA1.

Circulating miR-210 levels have been shown to have diagnostic value in DLBCL, pancreatic cancer, bladder cancer, glioma, liver carcinoma, and renal carcinoma and with the presence of metastasis in patients with breast cancer and pancreatic cancer. miR-210 has been also correlated with sensitivity to treatment in breast cancer and with prognosis in patients with breast cancer, pancreatic cancer, bladder cancer, and liver carcinoma.

2.13. miR-221/-222

miR-221 and its paralogue miR-222 are known to target angiogenesis by direct interaction with KIT, PTEN, TIMP3, ADAM10, and ADAM17 and by indirectly regulating endothelial nitric oxide synthase expression. miR-221/-222 have also been described as regulators of cell proliferation via the targeting of SEMA3B, IRF2, SOCS3, p27/CDKN1B, HECTD2, RAB1A, β-catenin/CTNNB1, TGFB1, ADAM17, ITGB4, and STAT3. Other pathways regulated by miR-221/-222 include apoptosis and metastasis via PTEN, IRF2, SOCS3, BBC3, SEMA3B, HECTD2, RAB1A, ADAM17, ITGB4, STAT5A, and Ecm29/KIAA0368; in resistance to chemotherapy in some type of cancers through PTEN and β-catenin/CTNNB1 regulation.

Circulating miR-221/-222 levels have been identified as diagnostic markers in prostate cancer, colorectal carcinoma, NK/T-cell lymphoma, liver carcinoma, larynx cancer, glioma, and melanoma. They also have prognostic value in glioma, melanoma, prostate cancer, and renal carcinoma.

2.14. miR-375

miR-375 is a tumor suppressor miRNA that has been described in different kind of cancers, where it targets genes related to proliferation and apoptosis (JAK2, PDK1, 14-3-3ζ, IGF1R, KLF4, KLF5, survivin, ERBB2, PIK3CA, MTDH, YAP1, CIP2A/KIAA1524, MTDH, and BCL2) as well as metastasis (IGF1R, CLDN1, CIP2A/KIAA1524, and BCL2) and mediates resistance to therapy (IGF1R, TP53, and PHLPP1). Furthermore, miR-375 is involved in epithelial to mesenchymal transition in breast cancer and targets ATG7 inhibiting autophagy and impairing the viability of cells under hypoxic conditions in liver cancer.

Circulating miR-375 has been identified as a diagnostic biomarker in oesophageal carcinoma, liver cancer, colorectal cancer, and lung cancer. Additionally, in prostate cancer, lung cancer, and oesophageal carcinoma, miR-375 has been shown to have prognostic value.

3. Extracellular miRNAs in Other Biological Fluids

In addition to blood, other biological fluids such as urine, saliva, cerebrospinal fluid, vitreous humor of the eye, breast milk, seminal fluid, and tears have been studied as potential sources of miRNA biomarkers (Figure 3). The majority of these studies concern tumor types associated with the source of the biological fluids. For example, saliva has been studied in head and neck squamous cell carcinoma, tumors of the parotid gland, esophageal cancer, and pancreatic cancer. Urine is another well studied source of cfmiRNAs associated with cancer in particular urological cancers including prostate and bladder cancer (reviewed in). In addition, several studies have looked at the potential of urine for miRNA biomarkers in ovarian, breast, and liver cancer. miRNAs in cerebrospinal fluid have been described as potential biomarkers for the diagnosis and monitoring of disease in brain tumors such as glioblastoma but also in CNS lymphomas and in brain metastases of non-neuronal origin. In a similar vein, miRNAs, in the vitreous humor of the eye, have been identified in ocular cancers including vitreoretinal lymphoma or uveal melanoma. It also has been suggested that the miRNA profile of breast milk could be a more sensitive biomarker for breast cancer than blood-associated miRNAs and that seminal fluid-associated miRNAs can serve as biomarkers of prostate cancer.

Challenges in Studying cfmiRNA

A major obstacle to the translation of cfmiRNAs from laboratory studies into the clinic is the lack of consistent and robust results with many apparently contradictory reports in the literature. A likely reason for this lack of reproducibility is that there are very few multi-center studies, and cohorts are often insufficiently powered. Another confounding factor is the fact that there is a high degree of inter-individual variability in the levels of cfmiRNAs, even when focusing only on healthy populations. Moreover, there is a technical source of variation between studies, such as the starting material used for the experiments (e.g., the purification of cells, the cell types, the control populations used, the RNA extraction method, etc.), the technological platforms (e.g., microarray, qRT-PCR vs. next generation sequencing (NGS) etc.), and the differing statistical methodologies used.

The blood collection and processing represent critical points of variability in cfmiRNA studies. In the first instance, miRNA contamination can occur at the venopuncture site itself. After extraction, the elapsed time between blood collection and processing should be minimized to prevent lysis and cellular contamination, which can be a major source of variability between samples. In addition, the choice of anti-coagulant used in plasma collection can influence downstream detection technologies, such as qRT-PCR and heparin-coated tubes, should be avoided. Another major source of difference in cfmiRNA profiles comes from the choice of whether to use serum or plasma, and whether to purify exosomes or use whole serum/plasma.

The choice of RNA purification procedure can also critically affect the results of cfmiRNA studies and should be considered carefully in terms of experimental design. For example, small RNA molecules with low GC content are known to be selectively lost during Trizol-based extraction (the most popular method) when present in low concentrations, such as in biological fluids, and thus should be avoided if possible; specific commercially available kits should be used instead. Many researchers use non-human miRNAs (e.g., C. elegans sequences) as spike-in controls to control for variability between the miRNA extraction efficiency between samples. Another important issue is that it is almost impossible to accurately quantify RNA in samples from biological fluids due to the low quantities of RNA present and the high levels of contaminating salts and protein that can interfere with spectrophotometric measurement. Therefore, studies often use fixed volumes of plasma to standardize, even if it is evident that they may contain different amounts of RNA.

There are many different methods available to measure cfmiRNAs, including qRT-PCR (LNA-based, Taqman or other proprietary technologies), digital PCR (dPCR), microarrays, and next generation sequencing (NGS) techniques. The choice of platform depends largely on the experimental design required (Figure 4). Importantly, it should be borne in mind that the choice of technique can massively influence measurements; indeed, several studies show a lack of concordance between platforms when using the same sample source.

Another challenging issue in cfmiRNA studies is the lack of consensus about a suitable endogenous reference to use in biological fluids, as the small nucleolar RNAs (snoRNAs) generally used as reference genes in miRNA cell-based studies is not present in biological fluids due to degradation. As an alternative, individual miRNAs themselves are frequently used. However, it has been shown that the expression levels of the most commonly used housekeeping miRNAs in cfmiRNA studies vary significantly between samples depending upon the pathology that is being studied. Therefore, miRNAs to be used as reference genes have to be chosen with care, determining empirically for each experiment which miRNAs are more stable (using geNorm and/or NormFinder algorithms), an approach taken by some studies but not always possible when sample volumes are limited. Alternatively, a more economical option is to include at least two (preferably three) miRNAs as reference controls for cfmiRNAs studies.

5. Conclusions

It is clear that there is a great deal of interest in liquid biopsies, and in cfmiRNA in particular, as a viable alternative to tissue-based sampling in the clinic. Such an approach would bring a fundamental change to cancer patient management by allowing repeated sampling for treatment response monitoring, an assessment of tumor heterogeneity, and even cancer screening programs. cfmiRNAs are particularly attractive candidates for non-invasive cancer biomarkers due to their surprising degree of stability in biological fluids; as we have outlined above, there is now a wealth of literature to suggest that this class of molecules holds great clinical promise. The caveat is that, as a very recently discovered field, there appears to be little agreement between seemingly identical studies, presumably due to many different factors outlined above between studies. In others words, there is a clear need of setting standardized approaches to be put into practicein future cfmiRNA biomarker studies if these molecules are to ever make their way into routine clinical practice.

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    Not in our library

  4. 4.

    Tan E.M., Schur P.H., Carr R.I., Kunkel H.G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J. Clin. Investig. 1966;45:1732-1740.

    Not in our library10.1172/jci105479

  5. 5.

    Ayala W., Moore L.V., Hess E.L. The purple color reaction given by diphenylamine reagent. I. With normal and rheumatic fever sera. J. Clin. Investig. 1951;30:781-785.

    Not in our library10.1172/jci102492

  6. 6.

    Leon S.A., Shapiro B., Sklaroff D.M., Yaros M.J. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 1977;37:646-650.

    Not in our library

  7. 7.

    Vasioukhin V., Anker P., Maurice P., Lyautey J., Lederrey C., Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br. J. Haematol. 1994;86:774-779.

    Not in our library10.1111/j.1365-2141.1994.tb04828.x

  8. 8.

    Sorenson G.D., Pribish D.M., Valone F.H., Memoli V.A., Bzik D.J., Yao S.L. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol. Biomark. Prev. 1994;3:67-71.

    Not in our library

  9. 9.

    Lo K.W., Lo Y.M., Leung S.F., Tsang Y.S., Chan L.Y., Johnson P.J., Hjelm N.M., Lee J.C., Huang D.P. Analysis of cell-free Epstein-Barr virus associated RNA in the plasma of patients with nasopharyngeal carcinoma. Clin. Chem. 1999;45:1292-1294.

    Not in our library

  10. 10.

    Lawrie C.H. MicroRNA expression in lymphoma. Expert Opin. Biol. Ther. 2007;7:1363-1374.

    Not in our library10.1517/14712598.7.9.1363

  11. 11.

    Lawrie C.H., Gal S., Dunlop H.M., Pushkaran B., Liggins A.P., Pulford K., Banham A.H., Pezzella F., Boultwood J., Wainscoat J.S., et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol. 2008;141:672-675.

    Not in our library10.1111/j.1365-2141.2008.07077.x

  12. 12.

    Mitchell P.S., Parkin R.K., Kroh E.M., Fritz B.R., Wyman S.K., Pogosova-Agadjanyan E.L., Peterson A., Noteboom J., O’Briant K.C., Allen A., et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA. 2008;105:10513-10518.

    Not in our library10.1073/pnas.0804549105

  13. 13.

    Lee R.C., Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001;294:862-864.

    Not in our library10.1126/science.1065329

  14. 14.

    Griffiths-Jones S., Grocock R.J., van Dongen S., Bateman A., Enright A.J. miRBase: MicroRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34:D140-D144.

    Not in our library10.1093/nar/gkj112

  15. 15.

    Friedman R.C., Farh K.K., Burge C.B., Bartel D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92-105.

    Not in our library10.1101/gr.082701.108

  16. 16.

    Kim V.N. MicroRNA biogenesis: Coordinated cropping and dicing. Nat. Rev. Mol. Cell Biol. 2005;6:376-385.

    Not in our library10.1038/nrm1644

  17. 17.

    Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 2000;100:57-70.

    Not in our library10.1016/s0092-8674(00)81683-9

  18. 18.

    Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646-674.

    Not in our library10.1016/j.cell.2011.02.013

  19. 19.

    Turchinovich A., Weiz L., Burwinkel B. Extracellular miRNAs: The mystery of their origin and function. Trends Biochem. Sci. 2012;37:460-465.

    Not in our library10.1016/j.tibs.2012.08.003

  20. 20.

    Cortez M.A., Bueso-Ramos C., Ferdin J., Lopez-Berestein G., Sood A.K., Calin G.A. MicroRNAs in body fluids—The mix of hormones and biomarkers. Nat. Rev. Clin. Oncol. 2011;8:467-477.

    Not in our library10.1038/nrclinonc.2011.76

  21. 21.

    Witwer K.W. Circulating microRNA biomarker studies: Pitfalls and potential solutions. Clin. Chem. 2015;61:56-63.

    Not in our library10.1373/clinchem.2014.221341

  22. 22.

    Turchinovich A., Weiz L., Langheinz A., Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39:7223-7233.

    Not in our library10.1093/nar/gkr254

  23. 23.

    Laterza O.F., Lim L., Garrett-Engele P.W., Vlasakova K., Muniappa N., Tanaka W.K., Johnson J.M., Sina J.F., Fare T.L., Sistare F.D., et al. Plasma microRNAs as sensitive and specific biomarkers of tissue injury. Clin. Chem. 2009;55:1977-1983.

    Not in our library10.1373/clinchem.2009.131797

  24. 24.

    Corsten M.F., Dennert R., Jochems S., Kuznetsova T., Devaux Y., Hofstra L., Wagner D.R., Staessen J.A., Heymans S., Schroen B. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ. Cardiovasc. Genet. 2010;3:499-506.

    Not in our library10.1161/circgenetics.110.957415

  25. 25.

    Gholamin S., Pasdar A., Khorrami M.S., Mirzaei H., Mirzaei H.R., Salehi R., Ferns G.A., Ghayour-Mobarhan M., Avan A. The potential for circulating microRNAs in the diagnosis of myocardial infarction: A novel approach to disease diagnosis and treatment. Curr. Pharm. Des. 2016;22:397-403.

    Not in our library10.2174/1381612822666151112151924

  26. 26.

    Sayed A.S., Xia K., Yang T.L., Peng J. Circulating microRNAs: A potential role in diagnosis and prognosis of acute myocardial infarction. Dis. Markers. 2013;35:561-566.

    Not in our library10.1155/2013/217948

  27. 27.

    Anker P., Mulcahy H., Stroun M. Circulating nucleic acids in plasma and serum as a noninvasive investigation for cancer: Time for large-scale clinical studies? Int. J. Cancer. 2003;103:149-152.

    Not in our library10.1002/ijc.10791

  28. 28.
    Detection of microRNA Expression in Human Peripheral Blood Microvesicles · 2008
    Corrected
  29. 29.

    Ismail N., Wang Y., Dakhlallah D., Moldovan L., Agarwal K., Batte K., Shah P., Wisler J., Eubank T.D., Tridandapani S., et al. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood. 2013;121:984-995.

    Not in our library10.1182/blood-2011-08-374793

  30. 30.

    Valadi H., Ekstrom K., Bossios A., Sjostrand M., Lee J.J., Lotvall J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007;9:654-659.

    Not in our library10.1038/ncb1596

  31. 31.

    Wang K., Zhang S., Weber J., Baxter D., Galas D.J. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 2010;38:7248-7259.

    Not in our library10.1093/nar/gkq601

  32. 32.

    Vickers K.C., Palmisano B.T., Shoucri B.M., Shamburek R.D., Remaley A.T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol. 2011;13:423-433.

    Not in our library10.1038/ncb2210

  33. 33.

    Arroyo J.D., Chevillet J.R., Kroh E.M., Ruf I.K., Pritchard C.C., Gibson D.F., Mitchell P.S., Bennett C.F., Pogosova-Agadjanyan E.L., Stirewalt D.L., et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. USA. 2011;108:5003-5008.

    Not in our library10.1073/pnas.1019055108

  34. 34.
    The Majority of MicroRNAs Detectable in Serum and Saliva Is Concentrated in Exosomes · 2012
    No notice
  35. 35.

    Mittelbrunn M., Gutierrez-Vazquez C., Villarroya-Beltri C., Gonzalez S., Sanchez-Cabo F., Gonzalez M.A., Bernad A., Sanchez-Madrid F. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2011;2:282.

    Not in our library10.1038/ncomms1285

  36. 36.

    Baulcombe D.C. RNA as a target and an initiator of post-transcriptional gene silencing in transgenic plants. Plant Mol. Biol. 1996;32:79-88.

    Not in our library10.1007/bf00039378

  37. 37.
    Circulating miRNAs: cell–cell communication function? · 2013
    No notice
  38. 38.

    Thery C. Exosomes: Secreted vesicles and intercellular communications. F1000 Biol. Rep. 2011;3:15.

    Not in our library10.3410/b3-15

  39. 39.

    Skog J., Wurdinger T., van Rijn S., Meijer D.H., Gainche L., Sena-Esteves M., Curry W.T., Carter B.S., Krichevsky A.M., Breakefield X.O. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 2008;10:1470-1476.

    Not in our library10.1038/ncb1800

  40. 40.

    Pegtel D.M., Cosmopoulos K., Thorley-Lawson D.A., van Eijndhoven M.A., Hopmans E.S., Lindenberg J.L., de Gruijl T.D., Wurdinger T., Middeldorp J.M. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA. 2010;107:6328-6333.

    Not in our library10.1073/pnas.0914843107

  41. 41.
    Transfer of MicroRNAs by Embryonic Stem Cell Microvesicles · 2009
    No notice
  42. 42.

    Mao L., Li J., Chen W.X., Cai Y.Q., Yu D.D., Zhong S.L., Zhao J.H., Zhou J.W., Tang J.H. Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs. Tumour Biol. 2015.

    Not in our library10.1007/s13277-015-4402-2

  43. 43.

    De Souza P.S., Faccion R.S., Bernardo P.S., Maia R.C. Membrane microparticles: Shedding new light into cancer cell communication. Cancer Res. Clin. Oncol. 2015.

    Not in our library10.1007/s00432-015-2029-8

  44. 44.

    Maushagen R., Pries R., Wollenberg B. Chemotherapy with paclitaxel leads to microRNA release. HNO. 2015;63:792-796.

    Not in our library10.1007/s00106-015-0080-z

  45. 45.
    Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA) · 2015
    No notice
  46. 46.

    Gai C., Carpanetto A., Deregibus M.C., Camussi G. Extracellular vesicle-mediated modulation of angiogenesis. Histol. Histopathol. 2015;34:11708.

    Not in our library10.14670/hh-11-708

  47. 47.

    Lu J., Getz G., Miska E.A., Alvarez-Saavedra E., Lamb J., Peck D., Sweet-Cordero A., Ebert B.L., Mak R.H., Ferrando A.A., et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834-838.

    Not in our library10.1038/nature03702

  48. 48.

    Lawrie C.H., Soneji S., Marafioti T., Cooper C.D., Palazzo S., Paterson J.C., Cattan H., Enver T., Mager R., Boultwood J., et al. MicroRNA expression distinguishes between germinal center B cell–like and activated B cell–like subtypes of diffuse large B cell lymphoma. Int. J. Cancer. 2007;121:1156-1161.

    Not in our library10.1002/ijc.22800

  49. 49.

    Mo M.H., Chen L., Fu Y., Wang W., Fu S.W. Cell-free Circulating miRNA Biomarkers in Cancer. J. Cancer. 2012;3:432-448.

    Not in our library10.7150/jca.4919

  50. 50.

    Chen X., Ba Y., Ma L., Cai X., Yin Y., Wang K., Guo J., Zhang Y., Chen J., Guo X., et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997-1006.

    Not in our library10.1038/cr.2008.282

  51. 51.

    Kosaka N., Iguchi H., Ochiya T. Circulating microRNA in body fluid: A new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101:2087-2092.

    Not in our library10.1111/j.1349-7006.2010.01650.x

  52. 52.

    Kelly B.D., Miller N., Sweeney K.J., Durkan G.C., Rogers E., Walsh K., Kerin M.J. A Circulating MicroRNA Signature as a Biomarker for Prostate Cancer in a High Risk Group. J. Clin. Med. 2015;4:1369-1379.

    Not in our library10.3390/jcm4071369

  53. 53.
    Circulating Exosomal microRNAs as Biomarkers of Colon Cancer · 2014
    No notice
  54. 54.

    Ghanbari R., Mosakhani N., Sarhadi V.K., Armengol G., Nouraee N., Mohammadkhani A., Khorrami S., Arefian E., Paryan M., Malekzadeh R., et al. Simultaneous Underexpression of let-7a-5p and let-7f-5p microRNAs in Plasma and Stool Samples from Early Stage Colorectal Carcinoma. Biomark. Cancer. 2015;7:39-48.

    Not in our library10.4137/bic.s25252

  55. 55.

    Zuo Z., Calin G.A., de Paula H.M., Medeiros L.J., Fernandez M.H., Shimizu M., Garcia-Manero G., Bueso-Ramos C.E. Circulating microRNAs let-7a and miR-16 predict progression-free survival and overall survival in patients with myelodysplastic syndrome. Blood. 2011;118:413-415.

    Not in our library10.1182/blood-2011-01-330704

  56. 56.
    Circulating microRNAs in plasma of patients with gastric cancers · 2010
    No notice
  57. 57.

    Heegaard N.H., Schetter A.J., Welsh J.A., Yoneda M., Bowman E.D., Harris C.C. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer. Int. J. Cancer. 2012;130:1378-1386.

    Not in our library10.1002/ijc.26153

  58. 58.

    Hung C.H., Hu T.H., Lu S.N., Kuo F.Y., Chen C.H., Wang J.H., Huang C.M., Lee C.M., Lin C.Y., Yen Y.H., et al. Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus. Int. J. Cancer. 2016;138:714-720.

    Not in our library10.1002/ijc.29802

  59. 59.

    Chung Y.W., Bae H.S., Song J.Y., Lee J.K., Lee N.W., Kim T., Lee K.W. Detection of microRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patients. Int. J. Gynecol. Cancer. 2013;23:673-679.

    Not in our library10.1097/igc.0b013e31828c166d

  60. 60.

    Dou H., Wang Y., Su G., Zhao S. Decreased plasma let-7c and miR-152 as noninvasive biomarker for non-small-cell lung cancer. Int. J. Clin. Exp. Med. 2015;8:9291-9298.

    Not in our library

  61. 61.

    Li X.X., Gao S.Y., Wang P.Y., Zhou X., Li Y.J., Yu Y., Yan Y.F., Zhang H.H., Lv C.J., Zhou H.H., et al. Reduced expression levels of let-7c in human breast cancer patients. Oncol. Lett. 2015;9:1207-1212.

    Not in our library10.3892/ol.2015.2877

  62. 62.

    Liu W.J., Xu Q., Sun L.P., Dong Q.G., He C.Y., Yuan Y. Expression of serum let-7c, let-7i, and let-7f microRNA with its target gene, pepsinogen C, in gastric cancer and precancerous disease. Tumour Biol. 2015;36:3337-3343.

    Not in our library10.1007/s13277-014-2967-9

  63. 63.

    Ali S., Almhanna K., Chen W., Philip P.A., Sarkar F.H. Differentially expressed miRNAs in the plasma may provide a molecular signature for aggressive pancreatic cancer. Am. J. Transl. Res. 2010;3:28-47.

    Not in our library

  64. 64.

    Kubiczkova L., Kryukov F., Slaby O., Dementyeva E., Jarkovsky J., Nekvindova J., Radova L., Greslikova H., Kuglik P., Vetesnikova E., et al. Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. Haematologica. 2014;99:511-518.

    Not in our library10.3324/haematol.2013.093500

  65. 65.

    Yu S., Liu Y., Wang J., Guo Z., Zhang Q., Yu F., Zhang Y., Huang K., Li Y., Song E., et al. Circulating microRNA profiles as potential biomarkers for diagnosis of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 2012;97:2084-2092.

    Not in our library10.1210/jc.2011-3059

  66. 66.
    Plasma miRNAs as Diagnostic and Prognostic Biomarkers for Ovarian Cancer · 2013
    No notice
  67. 67.

    Silva J., Garcia V., Zaballos A., Provencio M., Lombardia L., Almonacid L., Garcia J.M., Dominguez G., Pena C., Diaz R., et al. Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur. Respir. J. 2011;37:617-623.

    Not in our library10.1183/09031936.00029610

  68. 68.

    Ge W., Yu D.C., Li Q.G., Chen X., Zhang C.Y., Ding Y.T. Expression of serum miR-16, let-7f, and miR-21 in patients with hepatocellular carcinoma and their clinical significances. Clin. Lab. 2014;60:427-434.

    Not in our library10.7754/clin.lab.2013.130133

  69. 69.

    Huang J., Wu J., Li Y., Li X., Yang T., Yang Q., Jiang Y. Deregulation of serum microRNA expression is associated with cigarette smoking and lung cancer. BioMed Res. Int. 2014;2014:364316.

    Not in our library10.1155/2014/364316

  70. 70.

    Langhe R., Norris L., Saadeh F.A., Blackshields G., Varley R., Harrison A., Gleeson N., Spillane C., Martin C., O'Donnell D.M., et al. A novel serum microRNA panel to discriminate benign from malignant ovarian disease. Cancer Lett. 2015;356:628-636.

    Not in our library10.1016/j.canlet.2014.10.010

  71. 71.

    Anfossi S., Giordano A., Gao H., Cohen E.N., Tin S., Wu Q., Garza R.J., Debeb B.G., Alvarez R.H., Valero V., et al. High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2+ inflammatory breast cancer. PLoS ONE. 2014;9:627.

    Not in our library10.1371/journal.pone.0083113

  72. 72.
    Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer · 2010
    No notice
  73. 73.

    Teplyuk N.M., Mollenhauer B., Gabriely G., Giese A., Kim E., Smolsky M., Kim R.Y., Saria M.G., Pastorino S., Kesari S., et al. MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol. 2012;14:689-700.

    Not in our library10.1093/neuonc/nos074

  74. 74.

    Roth C., Kasimir-Bauer S., Pantel K., Schwarzenbach H. Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer. Mol. Oncol. 2011;5:281-291.

    Not in our library10.1016/j.molonc.2011.02.002

  75. 75.

    Xu H., Yao Y., Meng F., Qian X., Jiang X., Li X., Gao Z., Gao L. Predictive Value of Serum miR-10b, miR-29c, and miR-205 as Promising Biomarkers in Esophageal Squamous Cell Carcinoma Screening. Medicine (Baltimore). 2015;94:e1558.

    Not in our library10.1097/md.0000000000001558

  76. 76.

    Maclellan S.A., Lawson J., Baik J., Guillaud M., Poh C.F., Garnis C. Differential expression of miRNAs in the serum of patients with high-risk oral lesions. Cancer Med. 2012;1:268-274.

    Not in our library10.1002/cam4.17

  77. 77.
    Detection of Cancer with Serum miRNAs on an Oligonucleotide Microarray · 2009
    No notice
  78. 78.

    Mahn R., Heukamp L.C., Rogenhofer S., von Ruecker A., Muller S.C., Ellinger J. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 2011;77:1265.e9-1265.e16.

    Not in our library10.1016/j.urology.2011.01.020

  79. 79.

    Hu Z., Dong J., Wang L.E., Ma H., Liu J., Zhao Y., Tang J., Chen X., Dai J., Wei Q., et al. Serum microRNA profiling and breast cancer risk: The use of miR-484/191 as endogenous controls. Carcinogenesis. 2012;33:828-834.

    Not in our library10.1093/carcin/bgs030

  80. 80.

    Li H., Zhang K., Liu L.H., Ouyang Y., Guo H.B., Zhang H., Bu J., Xiao T. MicroRNA screening identifies circulating microRNAs as potential biomarkers for osteosarcoma. Oncol. Lett. 2015;10:1662-1668.

    Not in our library10.3892/ol.2015.3378

  81. 81.

    Zhang J., Song Y., Zhang C., Zhi X., Fu H., Ma Y., Chen Y., Pan F., Wang K., Ni J., et al. Circulating MiR-16–5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer. Theranostics. 2015;5:733-745.

    Not in our library10.7150/thno.10305

  82. 82.

    Wang H., Wang L., Wu Z., Sun R., Jin H., Ma J., Liu L., Ling R., Yi J., Wang L., et al. Three dysregulated microRNAs in serum as novel biomarkers for gastric cancer screening. Med. Oncol. 2014;31:298.

    Not in our library10.1007/s12032-014-0298-8

  83. 83.

    Li B.X., Yu Q., Shi Z.L., Li P., Fu S. Circulating microRNAs in esophageal squamous cell carcinoma: Association with locoregional staging and survival. Int. J. Clin. Exp. Med. 2015;8:7241-7250.

    Not in our library

  84. 84.

    Hirajima S., Komatsu S., Ichikawa D., Takeshita H., Konishi H., Shiozaki A., Morimura R., Tsujiura M., Nagata H., Kawaguchi T., et al. Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma. Br. J. Cancer. 2013;108:1822-1829.

    Not in our library10.1038/bjc.2013.148

  85. 85.

    Tsujiura M., Komatsu S., Ichikawa D., Shiozaki A., Konishi H., Takeshita H., Moriumura R., Nagata H., Kawaguchi T., Hirajima S., et al. Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer. Gastric Cancer. 2015;18:271-279.

    Not in our library10.1007/s10120-014-0363-1

  86. 86.

    Kodahl A.R., Lyng M.B., Binder H., Cold S., Gravgaard K., Knoop A.S., Ditzel H.J. Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: A case control study. Mol. Oncol. 2014;8:874-883.

    Not in our library10.1016/j.molonc.2014.03.002

  87. 87.

    Yau T.O., Wu C.W., Dong Y., Tang C.M., Ng S.S., Chan F.K., Sung J.J., Yu J. microRNA-221 and microRNA-18a identification in stool as potential biomarkers for the non-invasive diagnosis of colorectal carcinoma. Br. J. Cancer. 2014;111:1765-1771.

    Not in our library10.1038/bjc.2014.484

  88. 88.
    Detection of Exosomal miRNAs in the Plasma of Melanoma Patients · 2015
    No notice
  89. 89.

    Li Q., Liu M., Ma F., Luo Y., Cai R., Wang L., Xu N., Xu B. Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel. PLoS ONE. 2014;9:627.

    Not in our library10.1371/journal.pone.0104870

  90. 90.
    Oncogenic MicroRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum · 2014
    No notice
  91. 91.

    Feng Y., Liu J., Kang Y., He Y., Liang B., Yang P., Yu Z. miR-19a acts as an oncogenic microRNA and is up-regulated in bladder cancer. J. Exp. Clin. Cancer Res. 2014;33:67.

    Not in our library10.1186/s13046-014-0067-8

  92. 92.

    Matsumura T., Sugimachi K., Iinuma H., Takahashi Y., Kurashige J., Sawada G., Ueda M., Uchi R., Ueo H., Takano Y., et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br. J. Cancer. 2015;113:275-281.

    Not in our library10.1038/bjc.2015.201

  93. 93.

    Hao M., Zang M., Wendlandt E., Xu Y., An G., Gong D., Li F., Qi F., Zhang Y., Yang Y., et al. Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma. Int. J. Cancer. 2015;136:1835-1844.

    Not in our library10.1002/ijc.29199

  94. 94.

    Lin Q., Chen T., Lin Q., Lin G., Lin J., Chen G., Guo L. Serum miR-19a expression correlates with worse prognosis of patients with non-small cell lung cancer. J. Surg. Oncol. 2013;107:767-771.

    Not in our library10.1002/jso.23312

  95. 95.

    Wu C., Cao Y., He Z., He J., Hu C., Duan H., Jiang J. Serum levels of miR-19b and miR-146a as prognostic biomarkers for non-small cell lung cancer. Tohoku J. Exp. Med. 2014;232:85-95.

    Not in our library10.1620/tjem.232.85

  96. 96.

    Shen J., Hruby G.W., McKiernan J.M., Gurvich I., Lipsky M.J., Benson M.C., Santella R.M. Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer. Prostate. 2012;72:1469-1477.

    Not in our library10.1002/pros.22499

  97. 97.

    Geng Q., Fan T., Zhang B., Wang W., Xu Y., Hu H. Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer. Respir. Res. 2014;15:149.

    Not in our library10.1186/s12931-014-0149-3

  98. 98.

    Yau T.O., Wu C.W., Tang C.M., Chen Y., Fang J., Dong Y., Liang Q., Ng S.S., Chan F.K., Sung J.J., et al. MicroRNA-20a in human faeces as a non-invasive biomarker for colorectal cancer. Oncotarget. 2016;7:1559-1568.

    Not in our library10.18632/oncotarget.6403

  99. 99.

    He F.C., Meng W.W., Qu Y.H., Zhou M.X., He J., Lv P., Ming L. Expression of circulating microRNA-20a and let-7a in esophageal squamous cell carcinoma. World J. Gastroenterol. 2015;21:4660-4665.

    Not in our library10.3748/wjg.v21.i15.4660

  100. 100.

    Conev N.V., Donev I.S., Konsoulova-Kirova A.A., Chervenkov T.G., Kashlov J.K., Ivanov K.D. Serum expression levels of miR-17, miR-21, and miR-92 as potential biomarkers for recurrence after adjuvant chemotherapy in colon cancer patients. Biosci. Trends. 2016;9:393-401.

    Not in our library10.5582/bst.2015.01170

  101. 101.

    Ng E.K., Chong W.W., Jin H., Lam E.K., Shin V.Y., Yu J., Poon T.C., Ng S.S., Sung J.J. Differential expression of microRNAs in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut. 2009;58:1375-1381.

    Not in our library10.1136/gut.2008.167817

  102. 102.

    Resnick K.E., Alder H., Hagan J.P., Richardson D.L., Croce C.M., Cohn D.E. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol. Oncol. 2009;112:55-59.

    Not in our library10.1016/j.ygyno.2008.08.036

  103. 103.

    Huang Z., Huang D., Ni S., Peng Z., Sheng W., Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int. J. Cancer. 2010;127:118-126.

    Not in our library10.1002/ijc.25007

  104. 104.
    Down-Regulation of miR-92 in Human Plasma Is a Novel Marker for Acute Leukemia Patients · 2009
    No notice
  105. 105.

    Yuan R., Wang G., Zhi Q., Chen H., Han Y., Wang B., Kou Z., Hu H., Guo Z., Xue X., et al. Up-regulated circulating miR-106a by DNA methylation promised a potential diagnostic and prognostic marker for gastric cancer. Anticancer Agents Med. Chem. 2015.

    Not in our library10.2174/1871520615666150716110657

  106. 106.

    Koga Y., Yamazaki N., Yamamoto Y., Yamamoto S., Saito N., Kakugawa Y., Otake Y., Matsumoto M., Matsumura Y. Fecal miR-106a is a useful marker for colorectal cancer patients with false-negative results in immunochemical fecal occult blood test. Cancer Epidemiol. Biomark. Prev. 2013;22:1844-1852.

    Not in our library10.1158/1055-9965.epi-13-0512

  107. 107.

    Chen W.Y., Zhao X.J., Yu Z.F., Hu F.L., Liu Y.P., Cui B.B., Dong X.S., Zhao Y.S. The potential of plasma miRNAs for diagnosis and risk estimation of colorectal cancer. Int. J. Clin. Exp. Pathol. 2015;8:7092-7101.

    Not in our library

  108. 108.

    Li J., Liu Y., Wang C., Deng T., Liang H., Wang Y., Huang D., Fan Q., Wang X., Ning T., et al. Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma. Sci. Rep. 2015;5:12921.

    Not in our library10.1038/srep12921

  109. 109.

    Zeng Q., Jin C., Chen W., Xia F., Wang Q., Fan F., Du J., Guo Y., Lin C., Yang K., et al. Downregulation of serum miR-17 and miR-106b levels in gastric cancer and benign gastric diseases. Chin. J. Cancer Res. 2014;26:711-716.

    Not in our library10.3978/j.issn.1000-9604.2014.12.03

  110. 110.

    Jiang L., Li X., Cheng Q., Zhang B.H. Plasma microRNA might as a potential biomarker for hepatocellular carcinoma and chronic liver disease screening. Tumour Biol. 2015;36:7167-7174.

    Not in our library10.1007/s13277-015-3446-7

  111. 111.

    Sohn W., Kim J., Kang S.H., Yang S.R., Cho J.Y., Cho H.C., Shim S.G., Paik Y.H. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp. Mol. Med. 2015;47:e184.

    Not in our library10.1038/emm.2015.68

  112. 112.

    Zheng R., Pan L., Gao J., Ye X., Chen L., Zhang X., Tang W., Zheng W. Prognostic value of miR-106b expression in breast cancer patients. J. Surg. Res. 2015;195:158-165.

    Not in our library10.1016/j.jss.2014.12.035

  113. 113.

    Zhang R., Wang W., Li F., Zhang H., Liu J. MicroRNA-106b~25 expressions in tumor tissues and plasma of patients with gastric cancers. Med. Oncol. 2014;31:243.

    Not in our library10.1007/s12032-014-0243-x

  114. 114.

    Zhou X., Zhang X., Yang Y., Li Z., Du L., Dong Z., Qu A., Jiang X., Li P., Wang C. Urinary cell-free microRNA-106b as a novel biomarker for detection of bladder cancer. Med. Oncol. 2014;31:197.

    Not in our library10.1007/s12032-014-0197-z

  115. 115.

    Ji T., Zheng Z.G., Wang F.M., Xu L.J., Li L.F., Cheng Q.H., Guo J.F., Ding X.F. Differential microRNA expression by Solexa sequencing in the sera of ovarian cancer patients. Asian Pac. J. Cancer Prev. 2014;15:1739-1743.

    Not in our library10.7314/apjcp.2014.15.4.1739

  116. 116.

    Li J., Fu R., Yang L., Tu W. miR-21 expression predicts prognosis in diffuse large B-cell lymphoma. Int. J. Clin. Exp. Pathol. 2015;8:15019-15024.

    Not in our library

  117. 117.

    Chen W., Wang H., Chen H., Liu S., Lu H., Kong D., Huang X., Kong Q., Lu Z. Clinical significance and detection of microRNA-21 in serum of patients with diffuse large B-cell lymphoma in Chinese population. Eur. J. Haematol. 2014;92:407-412.

    Not in our library10.1111/ejh.12263

  118. 118.

    Jones K., Nourse J.P., Keane C., Bhatnagar A., Gandhi M.K. Plasma microRNA are disease response biomarkers in classical Hodgkin lymphoma. Clin. Cancer Res. 2014;20:253-264.

    Not in our library10.1158/1078-0432.ccr-13-1024

  119. 119.

    Mao X., Sun Y., Tang J. Serum miR-21 is a diagnostic and prognostic marker of primary central nervous system lymphoma. Neurol. Sci. 2014;35:233-238.

    Not in our library10.1007/s10072-013-1491-9

  120. 120.

    Kumar S., Keerthana R., Pazhanimuthu A., Perumal P. Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients. Indian J. Biochem. Biophys. 2013;50:210-214.

    Not in our library

  121. 121.

    Asaga S., Kuo C., Nguyen T., Terpenning M., Giuliano A.E., Hoon D.S. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin. Chem. 2011;57:84-91.

    Not in our library10.1373/clinchem.2010.151845

  122. 122.

    Toraih E.A., Mohammed E.A., Farrag S., Ramsis N., Hosny S. Pilot Study of Serum MicroRNA-21 as a Diagnostic and Prognostic Biomarker in Egyptian Breast Cancer Patients. Mol. Diagn. Ther. 2015;19:179-190.

    Not in our library10.1007/s40291-015-0143-6

  123. 123.

    Usmani A., Shoro A.A., Memon Z., Hussain M., Rehman R. Diagnostic, prognostic and predictive value of MicroRNA-21 in breast cancer patients, their daughters and healthy individuals. Am. J. Cancer Res. 2015;5:2484-2490.

    Not in our library

  124. 124.

    Wang G., Wang L., Sun S., Wu J., Wang Q. Quantitative measurement of serum microRNA-21 expression in relation to breast cancer metastasis in Chinese females. Ann. Lab. Med. 2015;35:226-232.

    Not in our library10.3343/alm.2015.35.2.226

  125. 125.

    Matamala N., Vargas M.T., Gonzalez-Campora R., Minambres R., Arias J.I., Menendez P., Andres-Leon E., Gomez-Lopez G., Yanowsky K., Calvete-Candenas J., et al. Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. Clin. Chem. 2015;61:1098-1106.

    Not in our library10.1373/clinchem.2015.238691

  126. 126.
    Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker · 2015
    No notice
  127. 127.

    Ma G.J., Gu R.M., Zhu M., Wen X., Li J.T., Zhang Y.Y., Zhang X.M., Chen S.Q. Plasma post-operative miR-21 expression in the prognosis of gastric cancers. Asian Pac. J. Cancer Prev. 2013;14:7551-7554.

    Not in our library10.7314/apjcp.2013.14.12.7551

  128. 128.

    Song J., Bai Z., Zhang J., Meng H., Cai J., Deng W., Bi J., Ma X., Zhang Z. Serum microRNA-21 levels are related to tumor size in gastric cancer patients but cannot predict prognosis. Oncol. Lett. 2013;6:1733-1737.

    Not in our library10.3892/ol.2013.1626

  129. 129.

    Kim S.Y., Jeon T.Y., Choi C.I., Kim D.H., Kim D.H., Kim G.H., Ryu D.Y., Lee B.E., Kim H.H. Validation of circulating miRNA biomarkers for predicting lymph node metastasis in gastric cancer. J. Mol. Diagn. 2013;15:661-669.

    Not in our library10.1016/j.jmoldx.2013.04.004

  130. 130.

    Shiotani A., Murao T., Kimura Y., Matsumoto H., Kamada T., Kusunoki H., Inoue K., Uedo N., Iishi H., Haruma K. Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer. Br. J. Cancer. 2013;109:2323-2330.

    Not in our library10.1038/bjc.2013.596

  131. 131.

    Komatsu S., Ichikawa D., Tsujiura M., Konishi H., Takeshita H., Nagata H., Kawaguchi T., Hirajima S., Arita T., Shiozaki A., et al. Prognostic impact of circulating miR-21 in the plasma of patients with gastric carcinoma. Anticancer Res. 2013;33:271-276.

    Not in our library

  132. 132.

    Wu J., Li G., Wang Z., Yao Y., Chen R., Pu X., Wang J. Circulating MicroRNA-21 Is a Potential Diagnostic Biomarker in Gastric Cancer. Dis. Markers. 2015;2015:435656.

    Not in our library10.1155/2015/435656

  133. 133.

    Ilhan-Mutlu A., Wagner L., Wohrer A., Furtner J., Widhalm G., Marosi C., Preusser M. Plasma MicroRNA-21 concentration may be a useful biomarker in glioblastoma patients. Cancer Investig. 2012;30:615-621.

    Not in our library10.3109/07357907.2012.708071

  134. 134.

    Xu Y.Z., Xi Q.H., Ge W.L., Zhang X.Q. Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer. Asian Pac. J. Cancer Prev. 2013;14:1057-1060.

    Not in our library10.7314/apjcp.2013.14.2.1057

  135. 135.

    Taylor D.D., Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol. 2008;110:13-21.

    Not in our library10.1016/j.ygyno.2008.04.033

  136. 136.

    Wang J., Chen J., Chang P., LeBlanc A., Li D., Abbruzzesse J.L., Frazier M.L., Killary A.M., Sen S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev. Res. (Phila). 2009;2:807-813.

    Not in our library10.1158/1940-6207.capr-09-0094

  137. 137.
    Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer · 2014
    No notice
  138. 138.

    Ali S., Dubaybo H., Brand R.E., Sarkar F.H. Differential Expression of MicroRNAs in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer. J. Cancer Sci. Ther. 2015;7:336-346.

    Not in our library10.4172/1948-5956.1000372

  139. 139.

    Yang J.Y., Sun Y.W., Liu D.J., Zhang J.F., Li J., Hua R. MicroRNAs in stool samples as potential screening biomarkers for pancreatic ductal adenocarcinoma cancer. Am. J. Cancer Res. 2014;4:663-673.

    Not in our library

  140. 140.
    Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma · 2013
    No notice
  141. 141.

    Pan W., Tang W., Yuan W., Yu Q., Zuo W., Xu C., Ma J. Expression and clinical significance of plasma small RNA in patients with pancreatic cancer. Zhonghua Zhong Liu Za Zhi. 2014;36:351-354.

    Not in our library

  142. 142.

    Humeau M., Vignolle-Vidoni A., Sicard F., Martins F., Bournet B., Buscail L., Torrisani J., Cordelier P. Salivary MicroRNA in Pancreatic Cancer Patients. PLoS ONE. 2015;10:627.

    Not in our library10.1371/journal.pone.0130996

  143. 143.

    Zhang H.L., Yang L.F., Zhu Y., Yao X.D., Zhang S.L., Dai B., Zhu Y.P., Shen Y.J., Shi G.H., Ye D.W. Serum miRNA-21: Elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate. 2011;71:326-331.

    Not in our library10.1002/pros.21246

  144. 144.

    Basati G., Emami Razavi A., Abdi S., Mirzaei A. Elevated level of microRNA-21 in the serum of patients with colorectal cancer. Med. Oncol. 2014;31:205.

    Not in our library10.1007/s12032-014-0205-3

  145. 145.

    Toiyama Y., Takahashi M., Hur K., Nagasaka T., Tanaka K., Inoue Y., Kusunoki M., Boland C.R., Goel A. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J. Natl. Cancer Inst. 2013;105:849-859.

    Not in our library10.1093/jnci/djt101

  146. 146.

    Liu G.H., Zhou Z.G., Chen R., Wang M.J., Zhou B., Li Y., Sun X.F. Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumour Biol. 2013;34:2175-2181.

    Not in our library10.1007/s13277-013-0753-8

  147. 147.

    Menendez P., Padilla D., Villarejo P., Palomino T., Nieto P., Menendez J.M., Rodriguez-Montes J.A. Prognostic implications of serum microRNA-21 in colorectal cancer. J. Surg. Oncol. 2013;108:369-373.

    Not in our library10.1002/jso.23415

  148. 148.

    Beckett E.L., Martin C., Choi J.H., King K., Niblett S., Boyd L., Duesing K., Yates Z., Veysey M., Lucock M. Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker. BBA Clin. 2015;4:45-51.

    Not in our library10.1016/j.bbacli.2015.06.006

  149. 149.

    Yang J.S., Li B.J., Lu H.W., Chen Y., Lu C., Zhu R.X., Liu S.H., Yi Q.T., Li J., Song C.H. Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening. Tumour Biol. 2015;36:3035-3042.

    Not in our library10.1007/s13277-014-2938-1

  150. 150.

    Kim J.O., Gazala S., Razzak R., Guo L., Ghosh S., Roa W.H., Bedard E.L. Non-small cell lung cancer detection using microRNA expression profiling of bronchoalveolar lavage fluid and sputum. Anticancer Res. 2015;35:1873-1880.

    Not in our library

  151. 151.

    Zhao W., Zhao J.J., Zhang L., Xu Q.F., Zhao Y.M., Shi X.Y., Xu A.G. Serum miR-21 level: A potential diagnostic and prognostic biomarker for non-small cell lung cancer. Int. J. Clin. Exp. Med. 2015;8:14759-14763.

    Not in our library

  152. 152.

    Hsu C.M., Lin P.M., Wang Y.M., Chen Z.J., Lin S.F., Yang M.Y. Circulating miRNA is a novel marker for head and neck squamous cell carcinoma. Tumour Biol. 2012;33:1933-1942.

    Not in our library10.1007/s13277-012-0454-8

  153. 153.
    Circulating microRNAs in plasma of patients with oesophageal squamous cell carcinoma · 2011
    No notice
  154. 154.
    Salivary MicroRNAs as Promising Biomarkers for Detection of Esophageal Cancer · 2013
    No notice
  155. 155.

    Zhuang C., Jiang W., Huang D., Xu L., Yang Q., Zheng L., Wang X., Hu L. Serum miR-21, miR-26a and miR-101 as potential biomarkers of hepatocellular carcinoma. Clin. Res. Hepatol. Gastroenterol. 2015.

    Not in our library10.1016/j.clinre.2015.11.002

  156. 156.

    Yin J., Bai Z., Song J., Yang Y., Wang J., Han W., Zhang J., Meng H., Ma X., Yang Y., et al. Differential expression of serum miR-126, miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer. Chin. J. Cancer Res. 2014;26:95-103.

    Not in our library10.3978/j.issn.1000-9604.2014.02.07

  157. 157.
    Expression of Serum Exosomal MicroRNA-21 in Human Hepatocellular Carcinoma · 2014
    No notice
  158. 158.

    Amr K.S., Ezzat W.M., Elhosary Y.A., Hegazy A.E., Fahim H.H., Kamel R.R. The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma. Gene. 2016;575:66-70.

    Not in our library10.1016/j.gene.2015.08.038

  159. 159.

    Kishimoto T., Eguchi H., Nagano H., Kobayashi S., Akita H., Hama N., Wada H., Kawamoto K., Tomokuni A., Tomimaru Y., et al. Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer. Cancer Sci. 2013;104:1626-1631.

    Not in our library10.1111/cas.12300

  160. 160.

    Liu X., Luo H.N., Tian W.D., Lu J., Li G., Wang L., Zhang B., Liang B.J., Peng X.H., Lin S.X., et al. Diagnostic and prognostic value of plasma microRNA deregulation in nasopharyngeal carcinoma. Cancer Biol. Ther. 2013;14:1133-1142.

    Not in our library10.4161/cbt.26170

  161. 161.

    Ouyang L., Liu P., Yang S., Ye S., Xu W., Liu X. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med. Oncol. 2013;30:340.

    Not in our library10.1007/s12032-012-0340-7

  162. 162.

    Hong Q., Fang J., Pang Y., Zheng J. Prognostic value of the microRNA-29 family in patients with primary osteosarcomas. Med. Oncol. 2014;31:37.

    Not in our library10.1007/s12032-014-0037-1

  163. 163.

    Wang L.G., Gu J. Serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis. Cancer Epidemiol. 2012;36:e61-e67.

    Not in our library10.1016/j.canep.2011.05.002

  164. 164.

    Brunet Vega A., Pericay C., Moya I., Ferrer A., Dotor E., Pisa A., Casalots A., Serra-Aracil X., Oliva J.C., Ruiz A., et al. microRNA expression profile in stage III colorectal cancer: Circulating miR-18a and miR-29a as promising biomarkers. Oncol. Rep. 2013;30:320-326.

    Not in our library10.3892/or.2013.2475

  165. 165.

    Wu Q., Wang C., Lu Z., Guo L., Ge Q. Analysis of serum genome-wide microRNAs for breast cancer detection. Clin. Chim. Acta. 2012;413:1058-1065.

    Not in our library10.1016/j.cca.2012.02.016

  166. 166.

    Wu Q., Lu Z., Li H., Lu J., Guo L., Ge Q. Next-generation sequencing of microRNAs for breast cancer detection. J. Biomed. Biotechnol. 2011;2011:597145.

    Not in our library10.1155/2011/597145

  167. 167.

    Basati G., Razavi A.E., Pakzad I., Malayeri F.A. Circulating levels of the miRNAs, miR-194, and miR-29b, as clinically useful biomarkers for colorectal cancer. Tumour Biol. 2015.

    Not in our library10.1007/s13277-015-3967-0

  168. 168.
    The functional significance of microRNA-29c in patients with colorectal cancer: a potential circulating biomarker for predicting early relapse. · 2013
    Not checked
  169. 169.
    Expression of miR-29c, miR-93, and miR-429 as Potential Biomarkers for Detection of Early Stage Non-Small Lung Cancer · 2014
    No notice
  170. 170.
    Circulating miR-17, miR-20a, miR-29c, and miR-223 Combined as Non-Invasive Biomarkers in Nasopharyngeal Carcinoma · 2012
    No notice
  171. 171.

    Cazzoli R., Buttitta F., di Nicola M., Malatesta S., Marchetti A., Rom W.N., Pass H.I. MicroRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J. Thorac. Oncol. 2013;8:1156-1162.

    Not in our library10.1097/jto.0b013e318299ac32

  172. 172.

    Chiam K., Wang T., Watson D.I., Mayne G.C., Irvine T.S., Bright T., Smith L., White I.A., Bowen J.M., Keefe D., et al. Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma. J. Gastrointest. Surg. 2015;19:1208-1215.

    Not in our library10.1007/s11605-015-2829-9

  173. 173.

    Chen Z.H., Zhang G.L., Li H.R., Luo J.D., Li Z.X., Chen G.M., Yang J. A panel of five circulating microRNAs as potential biomarkers for prostate cancer. Prostate. 2012;72:1443-1452.

    Not in our library10.1002/pros.22495

  174. 174.

    Kachakova D., Mitkova A., Popov E., Popov I., Vlahova A., Dikov T., Christova S., Mitev V., Slavov C., Kaneva R. Combinations of serum prostate-specific antigen and plasma expression levels of let-7c, miR-30c, miR-141, and miR-375 as potential better diagnostic biomarkers for prostate cancer. DNA Cell Biol. 2015;34:189-200.

    Not in our library10.1089/dna.2014.2663

  175. 175.

    Rani S., Gately K., Crown J., O’Byrne K., O’Driscoll L. Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma. Cancer Biol. Ther. 2013;14:1104-1112.

    Not in our library10.4161/cbt.26370

  176. 176.

    Le H.B., Zhu W.Y., Chen D.D., He J.Y., Huang Y.Y., Liu X.G., Zhang Y.K. Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients. Med. Oncol. 2012;29:3190-3197.

    Not in our library10.1007/s12032-012-0303-z

  177. 177.

    Hu Z., Chen X., Zhao Y., Tian T., Jin G., Shu Y., Chen Y., Xu L., Zen K., Zhang C., et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol. 2010;28:1721-1726.

    Not in our library10.1200/jco.2009.24.9342

  178. 178.

    Bhattacharya S., Steele R., Shrivastava S., Chakraborty S., di Bisceglie A.M., Ray R.B. Serum miR-30e and miR-223 as Novel Noninvasive Biomarkers for Hepatocellular Carcinoma. Am. J. Pathol. 2016;186:242-247.

    Not in our library10.1016/j.ajpath.2015.10.003

  179. 179.

    Franchina T., Amodeo V., Bronte G., Savio G., Ricciardi G.R., Picciotto M., Russo A., Giordano A., Adamo V. Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non-small cell lung cancer. J. Cell. Physiol. 2014;229:97-99.

    Not in our library10.1002/jcp.24422

  180. 180.

    Tian Q., Jia J., Ling S., Liu Y., Yang S., Shao Z. A causal role for circulating miR-34b in osteosarcoma. Eur. J. Surg. Oncol. 2014;40:67-72.

    Not in our library10.1016/j.ejso.2013.08.024

  181. 181.

    Liu X., Feng J., Tang L., Liao L., Xu Q., Zhu S. The regulation and function of miR-21-FOXO3a-miR-34b/c signaling in breast cancer. Int. J. Mol. Sci. 2015;16:3148-3162.

    Not in our library10.3390/ijms16023148

  182. 182.

    Liu F., Wang X., Li J., Gu K., Lv L., Zhang S., Che D., Cao J., Jin S., Yu Y. MiR-34c-3p functions as a tumour suppressor by inhibiting eIF4E expression in non-small cell lung cancer. Cell Prolif. 2015;48:582-592.

    Not in our library10.1111/cpr.12201

  183. 183.

    Park N.J., Zhou H., Elashoff D., Henson B.S., Kastratovic D.A., Abemayor E., Wong D.T. Salivary microRNA: Discovery, characterization, and clinical utility for oral cancer detection. Clin. Cancer Res. 2009;15:5473-5477.

    Not in our library10.1158/1078-0432.ccr-09-0736

  184. 184.

    Wang R.J., Zheng Y.H., Wang P., Zhang J.Z. Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer. Int. J. Clin. Exp. Pathol. 2015;8:765-771.

    Not in our library

  185. 185.

    Hsieh T.H., Hsu C.Y., Tsai C.F., Long C.Y., Chai C.Y., Hou M.F., Lee J.N., Wu D.C., Wang S.C., Tsai E.M. miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis. Oncotarget. 2015;6:494-509.

    Not in our library10.18632/oncotarget.2674

  186. 186.

    Zheng J., Zhou Z., Xu Z., Li G., Dong P., Chen Z., Lin D., Chen B., Yu F. Serum microRNA-125a-5p, a useful biomarker in liver diseases, correlates with disease progression. Mol. Med. Rep. 2015;12:1584-1590.

    Not in our library10.3892/mmr.2015.3546

  187. 187.
    Circulating MiR-125b as a Marker Predicting Chemoresistance in Breast Cancer · 2012
    No notice
  188. 188.

    Yuxia M., Zhennan T., Wei Z. Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis. J. Cancer Res. Clin. Oncol. 2012;138:2045-2050.

    Not in our library10.1007/s00432-012-1285-0

  189. 189.

    Cui E.H., Li H.J., Hua F., Wang B., Mao W., Feng X.R., Li J.Y., Wang X. Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy. Acta Pharmacol. Sin. 2013;34:309-313.

    Not in our library10.1038/aps.2012.125

  190. 190.

    Gu W.L., Ye D.X., Wu J.J. Expression and clinical significance of plasma microRNA-125b level in patients with oral squamous cell carcinoma. Shanghai Kou Qiang Yi Xue. 2015;24:71-75.

    Not in our library

  191. 191.

    Yamada A., Horimatsu T., Okugawa Y., Nishida N., Honjo H., Ida H., Kou T., Kusaka T., Sasaki Y., Yagi M., et al. Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia. Clin. Cancer Res. 2015;21:4234-4242.

    Not in our library10.1158/1078-0432.ccr-14-2793

  192. 192.

    Wei X., Chen D., Lv T., Li G., Qu S. Serum MicroRNA-125b as a Potential Biomarker for Glioma Diagnosis. Mol. Neurobiol. 2016;53:163-170.

    Not in our library10.1007/s12035-014-8993-1

  193. 193.

    Alegre E., Sanmamed M.F., Rodriguez C., Carranza O., Martin-Algarra S., Gonzalez A. Study of circulating microRNA-125b levels in serum exosomes in advanced melanoma. Arch. Pathol. Lab. Med. 2014;138:828-832.

    Not in our library10.5858/arpa.2013-0134-oa

  194. 194.

    Wang F., Hou J., Jin W., Li J., Yue Y., Jin H., Wang X. Increased circulating microRNA-155 as a potential biomarker for breast cancer screening: A meta-analysis. Molecules. 2014;19:6282-6293.

    Not in our library10.3390/molecules19056282

  195. 195.

    Liu J., Mao Q., Liu Y., Hao X., Zhang S., Zhang J. Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients. Chin. J. Cancer Res. 2013;25:46-54.

    Not in our library10.3978/j.issn.1000-9604.2012.11.04

  196. 196.
    Serum MicroRNA-155 as a Potential Biomarker to Track Disease in Breast Cancer · 2012
    No notice
  197. 197.

    Eichelser C., Flesch-Janys D., Chang-Claude J., Pantel K., Schwarzenbach H. Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression. Clin. Chem. 2013;59:1489-1496.

    Not in our library10.1373/clinchem.2013.205161

  198. 198.

    Lv Z.C., Fan Y.S., Chen H.B., Zhao D.W. Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer. Tumour Biol. 2015;36:1619-1625.

    Not in our library10.1007/s13277-014-2760-9

  199. 199.

    Gao F., Chang J., Wang H., Zhang G. Potential diagnostic value of miR-155 in serum from lung adenocarcinoma patients. Oncol. Rep. 2014;31:351-357.

    Not in our library10.3892/or.2013.2830

  200. 200.

    Liu R., Liao J., Yang M., Shi Y., Peng Y., Wang Y., Pan E., Guo W., Pu Y., Yin L. Circulating miR-155 expression in plasma: A potential biomarker for early diagnosis of esophageal cancer in humans. J. Toxicol. Environ. Health A. 2012;75:1154-1162.

    Not in our library10.1080/15287394.2012.699856

  201. 201.

    Zhi F., Cao X., Xie X., Wang B., Dong W., Gu W., Ling Y., Wang R., Yang Y., Liu Y. Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia. PLoS ONE. 2013;8:627.

    Not in our library10.1371/journal.pone.0056718

  202. 202.

    Fang C., Zhu D.X., Dong H.J., Zhou Z.J., Wang Y.H., Liu L., Fan L., Miao K.R., Liu P., Xu W., et al. Serum microRNAs are promising novel biomarkers for diffuse large B cell lymphoma. Ann. Hematol. 2012;91:553-559.

    Not in our library10.1007/s00277-011-1350-9

  203. 203.

    Ferrajoli A., Shanafelt T.D., Ivan C., Shimizu M., Rabe K.G., Nouraee N., Ikuo M., Ghosh A.K., Lerner S., Rassenti L.Z., et al. Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood. 2013;122:1891-1899.

    Not in our library10.1182/blood-2013-01-478222

  204. 204.

    Ishihara K., Sasaki D., Tsuruda K., Inokuchi N., Nagai K., Hasegawa H., Yanagihara K., Kamihira S. Impact of miR-155 and miR-126 as novel biomarkers on the assessment of disease progression and prognosis in adult T-cell leukemia. Cancer Epidemiol. 2012;36:560-565.

    Not in our library10.1016/j.canep.2012.07.002

  205. 205.

    Zuberi M., Mir R., Das J., Ahmad I., Javid J., Yadav P., Masroor M., Ahmad S., Ray P.C., Saxena A. Expression of serum miR-200a, miR-200b, and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features. Clin. Transl. Oncol. 2015;17:779-787.

    Not in our library10.1007/s12094-015-1303-1

  206. 206.
    Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer · 2012
    No notice
  207. 207.

    Antolin S., Calvo L., Blanco-Calvo M., Santiago M.P., Lorenzo-Patino M.J., Haz-Conde M., Santamarina I., Figueroa A., Anton-Aparicio L.M., Valladares-Ayerbes M. Circulating miR-200c and miR-141 and outcomes in patients with breast cancer. BMC Cancer. 2015;15:627.

    Not in our library10.1186/s12885-015-1238-5

  208. 208.

    Gao Y.C., Wu J. MicroRNA-200c and microRNA-141 as potential diagnostic and prognostic biomarkers for ovarian cancer. Tumour Biol. 2015;36:4843-4850.

    Not in our library10.1007/s13277-015-3138-3

  209. 209.

    Lin H.M., Castillo L., Mahon K.L., Chiam K., Lee B.Y., Nguyen Q., Boyer M.J., Stockler M.R., Pavlakis N., Marx G., et al. Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer. Br. J. Cancer. 2014;110:2462-2471.

    Not in our library10.1038/bjc.2014.181

  210. 210.

    Zhang G.J., Zhou T., Liu Z.L., Tian H.P., Xia S.S. Plasma miR-200c and miR-18a as potential biomarkers for the detection of colorectal carcinoma. Mol. Clin. Oncol. 2013;1:379-384.

    Not in our library10.3892/mco.2013.61

  211. 211.

    Toiyama Y., Hur K., Tanaka K., Inoue Y., Kusunoki M., Boland C.R., Goel A. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann. Surg. 2014;259:735-743.

    Not in our library10.1097/sla.0b013e3182a6909d

  212. 212.

    Zhang H.P., Sun F.B., Li S.J. Serum miR-200c expression level as a prognostic biomarker for gastric cancer. Genet. Mol. Res. 2015;14:15913-15920.

    Not in our library10.4238/2015.december.7.2

  213. 213.
    Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer · 2012
    No notice
  214. 214.

    Liu X.G., Zhu W.Y., Huang Y.Y., Ma L.N., Zhou S.Q., Wang Y.K., Zeng F., Zhou J.H., Zhang Y.K. High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med. Oncol. 2012;29:618-626.

    Not in our library10.1007/s12032-011-9923-y

  215. 215.

    Tanaka K., Miyata H., Yamasaki M., Sugimura K., Takahashi T., Kurokawa Y., Nakajima K., Takiguchi S., Mori M., Doki Y. Circulating miR-200c levels significantly predict response to chemotherapy and prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer. Ann. Surg. Oncol. 2013;20:S607-S615.

    Not in our library10.1245/s10434-013-3093-4

  216. 216.

    Kriebel S., Schmidt D., Holdenrieder S., Goltz D., Kristiansen G., Moritz R., Fisang C., Muller S.C., Ellinger J. Analysis of tissue and serum microRNA expression in patients with upper urinary tract urothelial cancer. PLoS ONE. 2015;10:627.

    Not in our library10.1371/journal.pone.0117284

  217. 217.

    Brase J.C., Johannes M., Schlomm T., Falth M., Haese A., Steuber T., Beissbarth T., Kuner R., Sultmann H. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int. J. Cancer. 2011;128:608-616.

    Not in our library10.1002/ijc.25376

  218. 218.
    Changes in circulating microRNA levels associated with prostate cancer · 2012
    No notice
  219. 219.

    Li Z., Ma Y.Y., Wang J., Zeng X.F., Li R., Kang W., Hao X.K. Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Oncol. Targets Ther. 2016;9:139-148.

    Not in our library10.2147/ott.s95565

  220. 220.

    Zhang H.L., Qin X.J., Cao D.L., Zhu Y., Yao X.D., Zhang S.L., Dai B., Ye D.W. An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions. Asian J. Androl. 2013;15:231-235.

    Not in our library10.1038/aja.2012.116

  221. 221.
    Circulating Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon Cancer and Predicts Poor Prognosis · 2011
    No notice
  222. 222.

    Ho A.S., Huang X., Cao H., Christman-Skieller C., Bennewith K., Le Q.T., Koong A.C. Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer. Transl. Oncol. 2010;3:109-113.

    Not in our library10.1593/tlo.09256

  223. 223.

    Zhao A., Li G., Peoc’h M., Genin C., Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp. Mol. Pathol. 2013;94:115-120.

    Not in our library10.1016/j.yexmp.2012.10.005

  224. 224.

    Iwamoto H., Kanda Y., Sejima T., Osaki M., Okada F., Takenaka A. Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int. J. Oncol. 2014;44:53-58.

    Not in our library10.3892/ijo.2013.2169

  225. 225.

    Jung E.J., Santarpia L., Kim J., Esteva F.J., Moretti E., Buzdar A.U., di Leo A., Le X.F., Bast R.C., Park S.T., et al. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer. 2012;118:2603-2614.

    Not in our library10.1002/cncr.26565

  226. 226.

    Wang J., Raimondo M., Guha S., Chen J., Diao L., Dong X., Wallace M.B., Killary A.M., Frazier M.L., Woodward T.A., et al. Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer. J. Cancer. 2014;5:696-705.

    Not in our library10.7150/jca.10094

  227. 227.
    Serum miR-210 Contributes to Tumor Detection, Stage Prediction and Dynamic Surveillance in Patients with Bladder Cancer. · 2015
    Not checked
  228. 228.

    Eissa S., Matboli M., Essawy N.O., Kotb Y.M. Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis. Tumour Biol. 2015;36:9545-9552.

    Not in our library10.1007/s13277-015-3722-6

  229. 229.

    Lai N.S., Wu D.G., Fang X.G., Lin Y.C., Chen S.S., Li Z.B., Xu S.S. Serum microRNA-210 as a potential noninvasive biomarker for the diagnosis and prognosis of glioma. Br. J. Cancer. 2015;112:1241-1246.

    Not in our library10.1038/bjc.2015.91

  230. 230.

    Zhan M., Li Y., Hu B., He X., Huang J., Zhao Y., Fu S., Lu L. Serum microRNA-210 as a predictive biomarker for treatment response and prognosis in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. J. Vasc. Int. Radiol. 2014;25:1279-1287.

    Not in our library10.1016/j.jvir.2014.04.013

  231. 231.

    Pu X.X., Huang G.L., Guo H.Q., Guo C.C., Li H., Ye S., Ling S., Jiang L., Tian Y., Lin T.Y. Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression. J. Gastroenterol. Hepatol. 2010;25:1674-1680.

    Not in our library10.1111/j.1440-1746.2010.06417.x

  232. 232.

    Guo H.Q., Huang G.L., Guo C.C., Pu X.X., Lin T.Y. Diagnostic and prognostic value of circulating miR-221 for extranodal natural killer/T-cell lymphoma. Dis. Markers. 2010;29:251-258.

    Not in our library10.1155/2010/474692

  233. 233.

    Yilmaz S.S., Guzel E., Karatas O.F., Yilmaz M., Creighton C.J., Ozen M. MiR-221 as a pre- and postoperative plasma biomarker for larynx cancer patients. Laryngoscope. 2015;125:E377-E381.

    Not in our library10.1002/lary.25332

  234. 234.

    Zhang R., Pang B., Xin T., Guo H., Xing Y., Xu S., Feng B., Liu B., Pang Q. Plasma miR-221/222 Family as Novel Descriptive and Prognostic Biomarkers for Glioma. Mol. Neurobiol. 2015.

    Not in our library10.1007/s12035-014-9079-9

  235. 235.

    Li P., He Q.Y., Luo C.Q., Qian L.Y. Circulating miR-221 expression level and prognosis of cutaneous malignant melanoma. Med. Sci. Monit. 2014;20:2472-2477.

    Not in our library10.12659/msm.891327

  236. 236.

    Teixeira A.L., Ferreira M., Silva J., Gomes M., Dias F., Santos J.I., Mauricio J., Lobo F., Medeiros R. Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumour Biol. 2014;35:4057-4066.

    Not in our library10.1007/s13277-013-1531-3

  237. 237.
    De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer · 2012
    No notice
  238. 238.

    Yu H., Jiang L., Sun C., Guo L., Lin M., Huang J., Zhu L. Decreased circulating miR-375: A potential biomarker for patients with non-small-cell lung cancer. Gene. 2014;534:60-65.

    Not in our library10.1016/j.gene.2013.10.024

  239. 239.

    Nguyen H.C., Xie W., Yang M., Hsieh C.L., Drouin S., Lee G.S., Kantoff P.W. Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer. Prostate. 2013;73:346-354.

    Not in our library10.1002/pros.22572

  240. 240.

    Huang X., Yuan T., Liang M., Du M., Xia S., Dittmar R., Wang D., See W., Costello B.A., Quevedo F., et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur. Urol. 2015;67:33-41.

    Not in our library10.1016/j.eururo.2014.07.035

  241. 241.

    Wu C., Li M., Hu C., Duan H. Clinical significance of serum miR-223, miR-25 and miR-375 in patients with esophageal squamous cell carcinoma. Mol. Biol. Rep. 2014;41:1257-1266.

    Not in our library10.1007/s11033-013-2970-z

  242. 242.

    Yin J., Hou P., Wu Z., Wang T., Nie Y. Circulating miR-375 and miR-199a-3p as potential biomarkers for the diagnosis of hepatocellular carcinoma. Tumour Biol. 2015;36:4501-4507.

    Not in our library10.1007/s13277-015-3092-0

  243. 243.

    Xu L., Li M., Wang M., Yan D., Feng G., An G. The expression of microRNA-375 in plasma and tissue is matched in human colorectal cancer. BMC Cancer. 2014;14:627.

    Not in our library10.1186/1471-2407-14-714

  244. 244.

    Roush S., Slack F.J. The let-7 family of microRNAs. Trends Cell Biol. 2008;18:505-516.

    Not in our library10.1016/j.tcb.2008.07.007

  245. 245.

    Boyerinas B., Park S.M., Hau A., Murmann A.E., Peter M.E. The role of let-7 in cell differentiation and cancer. Endocr. Relat. Cancer. 2010;17:F19-F36.

    Not in our library10.1677/erc-09-0184

  246. 246.

    Johnson S.M., Grosshans H., Shingara J., Byrom M., Jarvis R., Cheng A., Labourier E., Reinert K.L., Brown D., Slack F.J. RAS is regulated by the let-7 microRNA family. Cell. 2005;120:635-647.

    Not in our library10.1016/j.cell.2005.01.014

  247. 247.

    Kumar M.S., Erkeland S.J., Pester R.E., Chen C.Y., Ebert M.S., Sharp P.A., Jacks T. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc. Natl. Acad. Sci. USA. 2008;105:3903-3908.

    Not in our library10.1073/pnas.0712321105

  248. 248.

    Mayr C., Hemann M.T., Bartel D.P. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007;315:1576-1579.

    Not in our library10.1126/science.1137999

  249. 249.

    Lee Y.S., Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21:1025-1030.

    Not in our library10.1101/gad.1540407

  250. 250.

    Wang Y., Lu Y., Toh S.T., Sung W.K., Tan P., Chow P., Chung A.Y., Jooi L.L., Lee C.G. Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3. J. Hepatol. 2010;53:57-66.

    Not in our library10.1016/j.jhep.2009.12.043

  251. 251.

    He X., Duan C., Chen J., Ou-Yang X., Zhang Z., Li C., Peng H. Let-7a elevates p21(WAF1) levels by targeting of NIRF and suppresses the growth of A549 lung cancer cells. FEBS Lett. 2009;583:3501-3507.

    Not in our library10.1016/j.febslet.2009.10.007

  252. 252.

    Sampson V.B., Rong N.H., Han J., Yang Q., Aris V., Soteropoulos P., Petrelli N.J., Dunn S.P., Krueger L.J. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 2007;67:9762-9770.

    Not in our library10.1158/0008-5472.can-07-2462

  253. 253.

    Akao Y., Nakagawa Y., Naoe T. let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol. Pharm. Bull. 2006;29:903-906.

    Not in our library10.1248/bpb.29.903

  254. 254.

    Kim H.H., Kuwano Y., Srikantan S., Lee E.K., Martindale J.L., Gorospe M. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev. 2009;23:1743-1748.

    Not in our library10.1101/gad.1812509

  255. 255.

    Legesse-Miller A., Elemento O., Pfau S.J., Forman J.J., Tavazoie S., Coller H.A. Let-7 Overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of Wee1 kinase in primary fibroblasts. J. Biol. Chem. 2009;284:6605-6609.

    Not in our library10.1074/jbc.c900002200

  256. 256.

    Johnson C.D., Esquela-Kerscher A., Stefani G., Byrom M., Kelnar K., Ovcharenko D., Wilson M., Wang X., Shelton J., Shingara J., et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67:7713-7722.

    Not in our library10.1158/0008-5472.can-07-1083

  257. 257.

    Schultz J., Lorenz P., Gross G., Ibrahim S., Kunz M. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res. 2008;18:549-557.

    Not in our library10.1038/cr.2008.45

  258. 258.

    Tsang W.P., Kwok T.T. Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis. 2008;13:1215-1222.

    Not in our library10.1007/s10495-008-0256-z

  259. 259.

    Tokumaru S., Suzuki M., Yamada H., Nagino M., Takahashi T. Let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis. 2008;29:2073-2077.

    Not in our library10.1093/carcin/bgn187

  260. 260.

    Forman J.J., Legesse-Miller A., Coller H.A. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc. Natl. Acad. Sci. USA. 2008;105:14879-14884.

    Not in our library10.1073/pnas.0803230105

  261. 261.

    Cookson V.J., Bentley M.A., Hogan B.V., Horgan K., Hayward B.E., Hazelwood L.D., Hughes T.A. Circulating microRNA profiles reflect the presence of breast tumours but not the profiles of microRNAs within the tumours. Cell. Oncol. 2012;35:301-308.

    Not in our library10.1007/s13402-012-0089-1

  262. 262.
    Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia · 2013
    No notice
  263. 263.

    Joosse S.A., Muller V., Steinbach B., Pantel K., Schwarzenbach H. Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases. Br. J. Cancer. 2014;111:909-917.

    Not in our library10.1038/bjc.2014.360

  264. 264.

    Ma L., Teruya-Feldstein J., Weinberg R.A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682-688.

    Not in our library10.1038/nature06174

  265. 265.

    Sun L., Yan W., Wang Y., Sun G., Luo H., Zhang J., Wang X., You Y., Yang Z., Liu N. MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10. Brain Res. 2011;1389:9-18.

    Not in our library10.1016/j.brainres.2011.03.013

  266. 266.

    Tian Y., Luo A., Cai Y., Su Q., Ding F., Chen H., Liu Z. MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J. Biol. Chem. 2010;285:7986-7994.

    Not in our library10.1074/jbc.m109.062877

  267. 267.

    Ibrahim S.A., Yip G.W., Stock C., Pan J.W., Neubauer C., Poeter M., Pupjalis D., Koo C.Y., Kelsch R., Schule R., et al. Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a Rho-GTPase- and E-cadherin-dependent mechanism. Int. J. Cancer. 2012;131:E884-E896.

    Not in our library10.1002/ijc.27629

  268. 268.

    Liao C.G., Kong L.M., Zhou P., Yang X.L., Huang J.G., Zhang H.L., Lu N. miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs. J. Transl. Med. 2014;12:234.

    Not in our library10.1186/s12967-014-0234-x

  269. 269.

    Liu Z., Zhu J., Cao H., Ren H., Fang X. miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer. Int. J. Oncol. 2012;40:1553-1560.

    Not in our library10.3892/ijo.2012.1342

  270. 270.

    Ma Z., Chen Y., Min L., Li L., Huang H., Li J., Yan Q., Song P., Dai L., Yao X. Augmented miR-10b expression associated with depressed expression of its target gene KLF4 involved in gastric carcinoma. Int. J. Clin. Exp. Pathol. 2015;8:5071-5079.

    Not in our library

  271. 271.

    Tsukerman P., Stern-Ginossar N., Gur C., Glasner A., Nachmani D., Bauman Y., Yamin R., Vitenshtein A., Stanietsky N., Bar-Mag T., et al. miR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells. Cancer Res. 2012;72:5463-5472.

    Not in our library10.1158/0008-5472.can-11-2671

  272. 272.

    Zhang L., Sun J., Wang B., Ren J.C., Su W., Zhang T. MicroRNA-10b Triggers the Epithelial-Mesenchymal Transition (EMT) of Laryngeal Carcinoma Hep-2 Cells by Directly Targeting the E-cadherin. Appl. Biochem. Biotechnol. 2015;176:33-44.

    Not in our library10.1007/s12010-015-1505-6

  273. 273.

    Teplyuk N.M., Uhlmann E.J., Wong A.H., Karmali P., Basu M., Gabriely G., Jain A., Wang Y., Chiocca E.A., Stephens R., et al. MicroRNA-10b inhibition reduces E2F1-mediated transcription and miR-15/16 activity in glioblastoma. Oncotarget. 2015;6:3770-3783.

    Not in our library10.18632/oncotarget.3009

  274. 274.

    Biagioni F., Bossel Ben-Moshe N., Fontemaggi G., Canu V., Mori F., Antoniani B., di Benedetto A., Santoro R., Germoni S., de Angelis F., et al. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours. EMBO Mol. Med. 2012;4:1214-1229.

    Not in our library10.1002/emmm.201201483

  275. 275.

    Liang H., Fu Z., Jiang X., Wang N., Wang F., Wang X., Zhang S., Wang Y., Yan X., Guan W.X., et al. miR-16 promotes the apoptosis of human cancer cells by targeting FEAT. BMC Cancer. 2015;15:627.

    Not in our library10.1186/s12885-015-1458-8

  276. 276.

    Chen L., Wang Q., Wang G.D., Wang H.S., Huang Y., Liu X.M., Cai X.H. miR-16 inhibits cell proliferation by targeting IGF1R and the Raf1-MEK1/2-ERK1/2 pathway in osteosarcoma. FEBS Lett. 2013;587:1366-1372.

    Not in our library10.1016/j.febslet.2013.03.007

  277. 277.

    Cai C.K., Zhao G.Y., Tian L.Y., Liu L., Yan K., Ma Y.L., Ji Z.W., Li X.X., Han K., Gao J., et al. miR-15a and miR-16–1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol. Rep. 2012;28:1764-1770.

    Not in our library10.3892/or.2012.1995

  278. 278.

    Yang T.Q., Lu X.J., Wu T.F., Ding D.D., Zhao Z.H., Chen G.L., Xie X.S., Li B., Wei Y.X., Guo L.C., et al. MicroRNA-16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor-κB1/MMP9 signaling pathway. Cancer Sci. 2014;105:265-271.

    Not in our library10.1111/cas.12351

  279. 279.

    Zhu Y., Xia Y., Niu H., Chen Y. miR-16 induced the suppression of cell apoptosis while promote proliferation in esophageal squamous cell carcinoma. Cell. Physiol. Biochem. 2014;33:1340-1348.

    Not in our library10.1159/000358701

  280. 280.

    He Q., Ren X., Chen J., Li Y., Tang X., Wen X., Yang X., Zhang J., Wang Y., Ma J., et al. miR-16 targets fibroblast growth factor 2 to inhibit NPC cell proliferation and invasion via PI3K/AKT and MAPK signaling pathways. Oncotarget. 2015.

    Not in our library10.18632/oncotarget.6504

  281. 281.

    Zubillaga-Guerrero M.I., Alarcon-Romero Ldel C., Illades-Aguiar B., Flores-Alfaro E., Bermudez-Morales V.H., Deas J., Peralta-Zaragoza O. MicroRNA miR-16-1 regulates CCNE1 (cyclin E1) gene expression in human cervical cancer cells. Int. J. Clin. Exp. Med. 2015;8:15999-16006.

    Not in our library

  282. 282.

    Ofir M., Hacohen D., Ginsberg D. miR-15 and miR-16 are direct transcriptional targets of E2F1 that limit E2F-induced proliferation by targeting cyclin E. Mol. Cancer Res. 2011;9:440-447.

    Not in our library10.1158/1541-7786.mcr-10-0344

  283. 283.

    Huang N., Wu J., Qiu W., Lyu Q., He J., Xie W., Xu N., Zhang Y. miR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin. Cancer Biol. Ther. 2015;16:941-948.

    Not in our library10.1080/15384047.2015.1040963

  284. 284.

    Renjie W., Haiqian L. miR-132, miR-15a and miR-16 synergistically inhibit pituitary tumor cell proliferation, invasion and migration by targeting Sox5. Cancer Lett. 2015;356:568-578.

    Not in our library10.1016/j.canlet.2014.10.003

  285. 285.

    Lewis B.P., Shih I.H., Jones-Rhoades M.W., Bartel D.P., Burge C.B. Prediction of mammalian microRNA targets. Cell. 2003;115:787-798.

    Not in our library10.1016/s0092-8674(03)01018-3

  286. 286.

    Takakura S., Mitsutake N., Nakashima M., Namba H., Saenko V.A., Rogounovitch T.I., Nakazawa Y., Hayashi T., Ohtsuru A., Yamashita S. Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci. 2008;99:1147-1154.

    Not in our library10.1111/j.1349-7006.2008.00800.x

  287. 287.

    Dews M., Fox J.L., Hultine S., Sundaram P., Wang W., Liu Y.Y., Furth E., Enders G.H., El-Deiry W., Schelter J.M., et al. The myc-miR-17~92 axis blunts TGFβ signaling and production of multiple TGF{beta}-dependent antiangiogenic factors. Cancer Res. 2010;70:8233-8246.

    Not in our library10.1158/0008-5472.can-10-2412

  288. 288.

    Mestdagh P., Bostrom A.K., Impens F., Fredlund E., van Peer G., de Antonellis P., von Stedingk K., Ghesquiere B., Schulte S., Dews M., et al. The miR-17–92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma. Mol. Cell. 2010;40:762-773.

    Not in our library10.1016/j.molcel.2010.11.038

  289. 289.

    Petrocca F., Vecchione A., Croce C.M. Emerging role of miR-106b-25/miR-17–92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008;68:8191-8194.

    Not in our library10.1158/0008-5472.can-08-1768

  290. 290.

    Sokolova V., Fiorino A., Zoni E., Crippa E., Reid J.F., Gariboldi M., Pierotti M.A. The Effects of miR-20a on p21: Two Mechanisms Blocking Growth Arrest in TGF-β-Responsive Colon Carcinoma. J. Cell. Physiol. 2015;230:3105-3114.

    Not in our library10.1002/jcp.25051

  291. 291.

    Hong L., Lai M., Chen M., Xie C., Liao R., Kang Y.J., Xiao C., Hu W.Y., Han J., Sun P. The miR-17–92 cluster of microRNAs confers tumorigenicity by inhibiting oncogene-induced senescence. Cancer Res. 2010;70:8547-8557.

    Not in our library10.1158/0008-5472.can-10-1938

  292. 292.

    Zhang G.J., Li J.S., Zhou H., Xiao H.X., Li Y., Zhou T. MicroRNA-106b promotes colorectal cancer cell migration and invasion by directly targeting DLC1. J. Exp. Clin. Cancer Res. 2015;34:73.

    Not in our library10.1186/s13046-015-0189-7

  293. 293.

    Li P., Xu Q., Zhang D., Li X., Han L., Lei J., Duan W., Ma Q., Wu Z., Wang Z. Upregulated miR-106a plays an oncogenic role in pancreatic cancer. FEBS Lett. 2014;588:705-712.

    Not in our library10.1016/j.febslet.2014.01.007

  294. 294.

    Wang Z., Wang B., Shi Y., Xu C., Xiao H.L., Ma L.N., Xu S.L., Yang L., Wang Q.L., Dang W.Q., et al. Oncogenic miR-20a and miR-106a enhance the invasiveness of human glioma stem cells by directly targeting TIMP-2. Oncogene. 2015;34:1407-1419.

    Not in our library10.1038/onc.2014.75

  295. 295.

    Woods K., Thomson J.M., Hammond S.M. Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J. Biol. Chem. 2007;282:2130-2134.

    Not in our library10.1074/jbc.c600252200

  296. 296.

    Prasad R., Katiyar S.K. Down-regulation of miRNA-106b inhibits growth of melanoma cells by promoting G1-phase cell cycle arrest and reactivation of p21/WAF1/Cip1 protein. Oncotarget. 2014;5:10636-10649.

    Not in our library10.18632/oncotarget.2527

  297. 297.

    Dews M., Homayouni A., Yu D., Murphy D., Sevignani C., Wentzel E., Furth E.E., Lee W.M., Enders G.H., Mendell J.T., et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat. Genet. 2006;38:1060-1065.

    Not in our library10.1038/ng1855

  298. 298.

    Zheng G., Du L., Yang X., Zhang X., Wang L., Yang Y., Li J., Wang C. Serum microRNA panel as biomarkers for early diagnosis of colorectal adenocarcinoma. Br. J. Cancer. 2014;111:1985-1992.

    Not in our library10.1038/bjc.2014.489

  299. 299.
    Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma. · 2011
    Not checked
  300. 300.

    Yoshizawa S., Ohyashiki J.H., Ohyashiki M., Umezu T., Suzuki K., Inagaki A., Iida S., Ohyashiki K. Downregulated plasma miR-92a levels have clinical impact on multiple myeloma and related disorders. Blood Cancer J. 2012;2:e53.

    Not in our library10.1038/bcj.2011.51

  301. 301.

    Wen Y., Han J., Chen J., Dong J., Xia Y., Liu J., Jiang Y., Dai J., Lu J., Jin G., et al. Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma. Int. J. Cancer. 2015;137:1679-1690.

    Not in our library10.1002/ijc.29544

  302. 302.

    Buscaglia L.E., Li Y. Apoptosis and the target genes of microRNA-21. Chin. J. Cancer. 2011;30:371-380.

    Not in our library10.5732/cjc.30.0371

  303. 303.

    Cmarik J.L., Min H., Hegamyer G., Zhan S., Kulesz-Martin M., Yoshinaga H., Matsuhashi S., Colburn N.H. Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proc. Natl. Acad. Sci. USA. 1999;96:14037-14042.

    Not in our library10.1073/pnas.96.24.14037

  304. 304.

    Jansen A.P., Camalier C.E., Colburn N.H. Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis. Cancer Res. 2005;65:6034-6041.

    Not in our library10.1158/0008-5472.can-04-2119

  305. 305.

    Leupold J.H., Yang H.S., Colburn N.H., Asangani I., Post S., Allgayer H. Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors. Oncogene. 2007;26:4550-4562.

    Not in our library10.1038/sj.onc.1210234

  306. 306.

    Papagiannakopoulos T., Shapiro A., Kosik K.S. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008;68:8164-8172.

    Not in our library10.1158/0008-5472.can-08-1305

  307. 307.

    Wickramasinghe N.S., Manavalan T.T., Dougherty S.M., Riggs K.A., Li Y., Klinge C.M. Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Res. 2009;37:2584-2595.

    Not in our library10.1093/nar/gkp117

  308. 308.

    Meng F., Henson R., Wehbe-Janek H., Ghoshal K., Jacob S.T., Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007;133:647-658.

    Not in our library10.1053/j.gastro.2007.05.022

  309. 309.
    MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway · 2015
    No notice
  310. 310.

    Gabriely G., Wurdinger T., Kesari S., Esau C.C., Burchard J., Linsley P.S., Krichevsky A.M. MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol. Cell. Biol. 2008;28:5369-5380.

    Not in our library10.1128/mcb.00479-08

  311. 311.
    MicroRNA-21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells · 2011
    No notice
  312. 312.

    Zhu S., Si M.L., Wu H., Mo Y.Y. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J. Biol. Chem. 2007;282:14328-14336.

    Not in our library10.1074/jbc.m611393200

  313. 313.

    Garzon R., Heaphy C.E., Havelange V., Fabbri M., Volinia S., Tsao T., Zanesi N., Kornblau S.M., Marcucci G., Calin G.A., et al. MicroRNA 29b functions in acute myeloid leukemia. Blood. 2009;114:5331-5341.

    Not in our library10.1182/blood-2009-03-211938

  314. 314.

    Oliveira L.H., Schiavinato J.L., Fraguas M.S., Lucena-Araujo A.R., Haddad R., Araujo A.G., Dalmazzo L.F., Rego E.M., Covas D.T., Zago M.A., et al. Potential roles of microRNA-29a in the molecular pathophysiology of T-cell acute lymphoblastic leukemia. Cancer Sci. 2015;106:1264-1277.

    Not in our library10.1111/cas.12766

  315. 315.

    Xu L., Xu Y., Jing Z., Wang X., Zha X., Zeng C., Chen S., Yang L., Luo G., Li B., et al. Altered expression pattern of miR-29a, miR-29b and the target genes in myeloid leukemia. Exp. Hematol. Oncol. 2014;3:17.

    Not in our library10.1186/2162-3619-3-17

  316. 316.

    Nguyen T., Kuo C., Nicholl M.B., Sim M.S., Turner R.R., Morton D.L., Hoon D.S. Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma. Epigenetics. 2011;6:388-394.

    Not in our library10.4161/epi.6.3.14056

  317. 317.

    Lin L.L., Wang W., Hu Z., Wang L.W., Chang J., Qian H. Negative feedback of miR-29 family TET1 involves in hepatocellular cancer. Med. Oncol. 2014;31:291.

    Not in our library10.1007/s12032-014-0291-2

  318. 318.

    Xiong Y., Fang J.H., Yun J.P., Yang J., Zhang Y., Jia W.H., Zhuang S.M. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010;51:836-845.

    Not in our library10.1002/hep.23380

  319. 319.

    Inoue A., Yamamoto H., Uemura M., Nishimura J., Hata T., Takemasa I., Ikenaga M., Ikeda M., Murata K., Mizushima T., et al. MicroRNA-29b is a Novel Prognostic Marker in Colorectal Cancer. Ann. Surg. Oncol. 2015;22:1410-1418.

    Not in our library10.1245/s10434-014-4255-8

  320. 320.

    Li Y., Wang F., Xu J., Ye F., Shen Y., Zhou J., Lu W., Wan X., Ma D., Xie X. Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29. J. Pathol. 2011;224:484-495.

    Not in our library10.1002/path.2873

  321. 321.

    Wu D.W., Hsu N.Y., Wang Y.C., Lee M.C., Cheng Y.W., Chen C.Y., Lee H. c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT. Oncogene. 2015;34:2072-2082.

    Not in our library10.1038/onc.2014.152

  322. 322.

    Nishikawa R., Goto Y., Kojima S., Enokida H., Chiyomaru T., Kinoshita T., Sakamoto S., Fuse M., Nakagawa M., Naya Y., et al. Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int. J. Oncol. 2014;45:401-410.

    Not in our library10.3892/ijo.2014.2437

  323. 323.

    Zhao J.J., Lin J., Lwin T., Yang H., Guo J., Kong W., Dessureault S., Moscinski L.C., Rezania D., Dalton W.S., et al. microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood. 2010;115:2630-2639.

    Not in our library10.1182/blood-2009-09-243147

  324. 324.

    Park S.Y., Lee J.H., Ha M., Nam J.W., Kim V.N. MiR-29 miRNAs activate p53 by targeting p85 α and CDC42. Nat. Struct. Mol. Biol. 2009;16:23-29.

    Not in our library10.1038/nsmb.1533

  325. 325.

    Ye Z., Zhao L., Li J., Chen W., Li X. MiR-30d Blocked Transforming Growth Factor β1-Induced Epithelial-Mesenchymal Transition by Targeting Snail in Ovarian Cancer Cells. Int. J. Gynecol. Cancer. 2015;25:1574-1581.

    Not in our library10.1097/igc.0000000000000546

  326. 326.

    Zhang N., Wang X., Huo Q., Sun M., Cai C., Liu Z., Hu G., Yang Q. MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin. Oncogene. 2014;33:3119-3128.

    Not in our library10.1038/onc.2013.286

  327. 327.

    Jiang B.Y., Zhang X.C., Su J., Meng W., Yang X.N., Yang J.J., Zhou Q., Chen Z.Y., Chen Z.H., Xie Z., et al. BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification. Mol. Cancer. 2013;12:61.

    Not in our library10.1186/1476-4598-12-61

  328. 328.
    miR-30a Suppresses Cell Migration and Invasion Through Downregulation of PIK3CD in Colorectal Carcinoma · 2013
    Not checked
  329. 329.

    Zhong K., Chen K., Han L., Li B. MicroRNA-30b/c inhibits non-small cell lung cancer cell proliferation by targeting Rab18. BMC Cancer. 2014;14:627.

    Not in our library10.1186/1471-2407-14-703

  330. 330.

    Zhang Q., Tang Q., Qin D., Yu L., Huang R., Lv G., Zou Z., Jiang X.C., Zou C., Liu W., et al. Role of microRNA 30a targeting insulin receptor substrate 2 in colorectal tumorigenesis. Mol. Cell. Biol. 2015;35:988-1000.

    Not in our library10.1128/mcb.01242-14

  331. 331.

    Wang T., Li F., Tang S. MiR-30a upregulates BCL2A1, IER3 and cyclin D2 expression by targeting FOXL2. Oncol. Lett. 2015;9:967-971.

    Not in our library10.3892/ol.2014.2723

  332. 332.

    Kao C.J., Martiniez A., Shi X.B., Yang J., Evans C.P., Dobi A., deVere White R.W., Kung H.J. miR-30 as a tumor suppressor connects EGF/Src signal to ERG and EMT. Oncogene. 2014;33:2495-2503.

    Not in our library10.1038/onc.2013.200

  333. 333.

    Ouzounova M., Vuong T., Ancey P.B., Ferrand M., Durand G., Le-Calvez Kelm F., Croce C., Matar C., Herceg Z., Hernandez-Vargas H. MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells. BMC Genom. 2013;14:627.

    Not in our library10.1186/1471-2164-14-139

  334. 334.

    Bridge G., Monteiro R., Henderson S., Emuss V., Lagos D., Georgopoulou D., Patient R., Boshoff C. The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 2012;120:5063-5072.

    Not in our library10.1182/blood-2012-04-423004

  335. 335.

    Maroof H., Salajegheh A., Smith R.A., Lam A.K. Role of microRNA-34 family in cancer with particular reference to cancer angiogenesis. Exp. Mol. Pathol. 2014;97:298-304.

    Not in our library10.1016/j.yexmp.2014.08.002

  336. 336.

    Ghandadi M., Sahebkar A. MicroRNA-34a and its target genes: Key factors in cancer multidrug resistance. Curr. Pharm. Des. 2016;22:933-939.

    Not in our library10.2174/1381612822666151209153729

  337. 337.
    miR-34 and p53: New Insights into a Complex Functional Relationship · 2015
    No notice
  338. 338.

    Choi Y.J., Lin C.P., Ho J.J., He X., Okada N., Bu P., Zhong Y., Kim S.Y., Bennett M.J., Chen C., et al. miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nat. Cell Biol. 2011;13:1353-1360.

    Not in our library10.1038/ncb2366

  339. 339.
    MiR-34a Targeting of Notch Ligand Delta-Like 1 Impairs CD15+/CD133+ Tumor-Propagating Cells and Supports Neural Differentiation in Medulloblastoma · 2011
    No notice
  340. 340.

    Cha Y.H., Kim N.H., Park C., Lee I., Kim H.S., Yook J.I. MiRNA-34 intrinsically links p53 tumor suppressor and Wnt signaling. Cell Cycle. 2012;11:1273-1281.

    Not in our library10.4161/cc.19618

  341. 341.

    Siemens H., Jackstadt R., Hunten S., Kaller M., Menssen A., Gotz U., Hermeking H. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle. 2011;10:4256-4271.

    Not in our library10.4161/cc.10.24.18552

  342. 342.

    Brzozowa M., Mielanczyk L., Michalski M., Malinowski L., Kowalczyk-Ziomek G., Helewski K., Harabin-Slowinska M., Wojnicz R. Role of Notch signaling pathway in gastric cancer pathogenesis. Contemp. Oncol. (Pozn). 2013;17:1-5.

    Not in our library10.5114/wo.2013.33765

  343. 343.

    Bae Y., Yang T., Zeng H.C., Campeau P.M., Chen Y., Bertin T., Dawson B.C., Munivez E., Tao J., Lee B.H. miRNA-34c regulates Notch signaling during bone development. Hum. Mol. Genet. 2012;21:2991-3000.

    Not in our library10.1093/hmg/dds129

  344. 344.

    Guan Y., Yao H., Zheng Z., Qiu G., Sun K. miR-125b targets BCL3 and suppresses ovarian cancer proliferation. Int. J. Cancer. 2011;128:2274-2283.

    Not in our library10.1002/ijc.25575

  345. 345.

    Huang L., Luo J., Cai Q., Pan Q., Zeng H., Guo Z., Dong W., Huang J., Lin T. MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3. Int. J. Cancer. 2011;128:1758-1769.

    Not in our library10.1002/ijc.25509

  346. 346.

    Li W., Duan R., Kooy F., Sherman S.L., Zhou W., Jin P. Germline mutation of microRNA-125a is associated with breast cancer. J. Med. Genet. 2009;46:358-360.

    Not in our library10.1136/jmg.2008.063123

  347. 347.

    Zhou M., Liu Z., Zhao Y., Ding Y., Liu H., Xi Y., Xiong W., Li G., Lu J., Fodstad O., et al. MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J. Biol. Chem. 2010;285:21496-21507.

    Not in our library10.1074/jbc.m109.083337

  348. 348.
    Ectopic Expression of MiR-125a Inhibits the Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting MMP11 and VEGF · 2012
    No notice
  349. 349.

    Liang L., Wong C.M., Ying Q., Fan D.N., Huang S., Ding J., Yao J., Yan M., Li J., Yao M., et al. MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2. Hepatology. 2010;52:1731-1740.

    Not in our library10.1002/hep.23904

  350. 350.

    Jia H.Y., Wang Y.X., Yan W.T., Li H.Y., Tian Y.Z., Wang S.M., Zhao H.L. MicroRNA-125b functions as a tumor suppressor in hepatocellular carcinoma cells. Int. J. Mol. Sci. 2012;13:8762-8774.

    Not in our library10.3390/ijms13078762

  351. 351.

    Kappelmann M., Kuphal S., Meister G., Vardimon L., Bosserhoff A.K. MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene. 2013;32:2984-2991.

    Not in our library10.1038/onc.2012.307

  352. 352.

    Xu N., Zhang L., Meisgen F., Harada M., Heilborn J., Homey B., Grander D., Stahle M., Sonkoly E., Pivarcsi A. MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. J. Biol. Chem. 2012;287:29899-29908.

    Not in our library10.1074/jbc.m112.391243

  353. 353.

    Liu L.H., Li H., Li J.P., Zhong H., Zhang H.C., Chen J., Xiao T. miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3. Biochem. Biophys. Res. Commun. 2011;416:31-38.

    Not in our library10.1016/j.bbrc.2011.10.117

  354. 354.

    Gong J., Zhang J.P., Li B., Zeng C., You K., Chen M.X., Yuan Y., Zhuang S.M. MicroRNA-125b promotes apoptosis by regulating the expression of Mcl-1, Bcl-w and IL-6R. Oncogene. 2013;32:3071-3079.

    Not in our library10.1038/onc.2012.318

  355. 355.

    Zhao A., Zeng Q., Xie X., Zhou J., Yue W., Li Y., Pei X. MicroRNA-125b induces cancer cell apoptosis through suppression of Bcl-2 expression. J. Genet. Genom. 2012;39:29-35.

    Not in our library10.1016/j.jgg.2011.12.003

  356. 356.

    Pang Y., Young C.Y., Yuan H. MicroRNAs and prostate cancer. Acta Biochim. Biophys. Sin. (Shanghai). 2010;42:363-369.

    Not in our library10.1093/abbs/gmq038

  357. 357.

    Mashima R. Physiological roles of miR-155. Immunology. 2015;145:323-333.

    Not in our library10.1111/imm.12468

  358. 358.

    Seddiki N., Brezar V., Ruffin N., Levy Y., Swaminathan S. Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology. 2014;142:32-38.

    Not in our library10.1111/imm.12227

  359. 359.

    George J., Lewis M.G., Renne R., Mattapallil J.J. Suppression of transforming growth factor beta receptor 2 and Smad5 is associated with high levels of microRNA miR-155 in the oral mucosa during chronic simian immunodeficiency virus infection. J. Virol. 2015;89:2972-2978.

    Not in our library10.1128/jvi.03248-14

  360. 360.
    MicroRNA-155 Modulates Treg and Th17 Cells Differentiation and Th17 Cell Function by Targeting SOCS1 · 2012
    No notice
  361. 361.

    Xue H., Hua L.M., Guo M., Luo J.M. SHIP1 is targeted by miR-155 in acute myeloid leukemia. Oncol. Rep. 2014;32:2253-2259.

    Not in our library10.3892/or.2014.3435

  362. 362.

    Salemi D., Cammarata G., Agueli C., Augugliaro L., Corrado C., Bica M.G., Raimondo S., Marfia A., Randazzo V., Dragotto P., et al. miR-155 regulative network in FLT3 mutated acute myeloid leukemia. Leuk. Res. 2015;39:883-896.

    Not in our library10.1016/j.leukres.2015.04.017

  363. 363.

    Wei Y., Zhu M., Corbalan-Campos J., Heyll K., Weber C., Schober A. Regulation of Csf1r and Bcl6 in macrophages mediates the stage-specific effects of microRNA-155 on atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2015;35:796-803.

    Not in our library10.1161/atvbaha.114.304723

  364. 364.

    De Santis R., Liepelt A., Mossanen J.C., Dueck A., Simons N., Mohs A., Trautwein C., Meister G., Marx G., Ostareck-Lederer A., et al. miR-155 targets Caspase-3 mRNA in activated macrophages. RNA Biol. 2016;13:43-58.

    Not in our library10.1080/15476286.2015.1109768

  365. 365.

    Wang H.Q., Yu X.D., Liu Z.H., Cheng X., Samartzis D., Jia L.T., Wu S.X., Huang J., Chen J., Luo Z.J. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J. Pathol. 2011;225:232-242.

    Not in our library10.1002/path.2931

  366. 366.

    Zang Y.S., Zhong Y.F., Fang Z., Li B., An J. miR-155 inhibits the sensitivity of lung cancer cells to cisplatin via negative regulation of Apaf-1 expression. Cancer Gene Ther. 2012;19:773-778.

    Not in our library10.1038/cgt.2012.60

  367. 367.

    Ling N., Gu J., Lei Z., Li M., Zhao J., Zhang H.T., Li X. MicroRNA-155 regulates cell proliferation and invasion by targeting FOXO3a in glioma. Oncol. Rep. 2013;30:2111-2118.

    Not in our library10.3892/or.2013.2685

  368. 368.

    Azimzadeh M., Rahaie M., Nasirizadeh N., Ashtari K., Naderi-Manesh H. An electrochemical nanobiosensor for plasma miRNA-155, based on graphene oxide and gold nanorod, for early detection of breast cancer. Biosens. Bioelectron. 2016;77:99-106.

    Not in our library10.1016/j.bios.2015.09.020

  369. 369.

    Paik W.H., Song B.J., Kim H.W., Kim H.R., Hwang J.H. MicroRNA-200c as a Prognostic Biomarker for Pancreatic Cancer. Korean J. Gastroenterol. 2015;66:215-220.

    Not in our library10.4166/kjg.2015.66.4.215

  370. 370.
    The Regulatory Role of MicroRNAs in EMT and Cancer · 2015
    No notice
  371. 371.

    Choi Y.C., Yoon S., Jeong Y., Yoon J., Baek K. Regulation of vascular endothelial growth factor signaling by miR-200b. Mol. Cells. 2011;32:77-82.

    Not in our library10.1007/s10059-011-1042-2

  372. 372.

    McArthur K., Feng B., Wu Y., Chen S., Chakrabarti S. MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes. 2011;60:1314-1323.

    Not in our library10.2337/db10-1557

  373. 373.

    Pecot C.V., Rupaimoole R., Yang D., Akbani R., Ivan C., Lu C., Wu S., Han H.D., Shah M.Y., Rodriguez-Aguayo C., et al. Tumour angiogenesis regulation by the miR-200 family. Nat. Commun. 2013;4:2427.

    Not in our library10.1038/ncomms3427

  374. 374.

    Wang X.L., Xie H.Y., Zhu C.D., Zhu X.F., Cao G.X., Chen X.H., Xu H.F. Increased miR-141 expression is associated with diagnosis and favorable prognosis of patients with bladder cancer. Tumour Biol. 2015;36:877-883.

    Not in our library10.1007/s13277-014-2656-8

  375. 375.

    Fasanaro P., D’Alessandra Y., di Stefano V., Melchionna R., Romani S., Pompilio G., Capogrossi M.C., Martelli F. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J. Biol. Chem. 2008;283:15878-15883.

    Not in our library10.1074/jbc.m800731200

  376. 376.

    Pulkkinen K., Malm T., Turunen M., Koistinaho J., Yla-Herttuala S. Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210. FEBS Lett. 2008;582:2397-2401.

    Not in our library10.1016/j.febslet.2008.05.048

  377. 377.

    Foekens J.A., Sieuwerts A.M., Smid M., Look M.P., de Weerd V., Boersma A.W., Klijn J.G., Wiemer E.A., Martens J.W. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc. Natl. Acad. Sci. USA. 2008;105:13021-13026.

    Not in our library10.1073/pnas.0803304105

  378. 378.

    Okamoto M., Nasu K., Abe W., Aoyagi Y., Kawano Y., Kai K., Moriyama M., Narahara H. Enhanced miR-210 expression promotes the pathogenesis of endometriosis through activation of signal transducer and activator of transcription 3. Hum. Reprod. 2015;30:632-641.

    Not in our library10.1093/humrep/deu332

  379. 379.

    Zhang Z., Sun H., Dai H., Walsh R.M., Imakura M., Schelter J., Burchard J., Dai X., Chang A.N., Diaz R.L., et al. MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle. 2009;8:2756-2768.

    Not in our library10.4161/cc.8.17.9387

  380. 380.

    Giannakakis A., Sandaltzopoulos R., Greshock J., Liang S., Huang J., Hasegawa K., Li C., O’Brien-Jenkins A., Katsaros D., Weber B.L., et al. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol. Ther. 2008;7:255-264.

    Not in our library10.4161/cbt.7.2.5297

  381. 381.

    Nakada C., Tsukamoto Y., Matsuura K., Nguyen T.L., Hijiya N., Uchida T., Sato F., Mimata H., Seto M., Moriyama M. Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells. J. Pathol. 2011;224:280-288.

    Not in our library10.1002/path.2860

  382. 382.

    Tsuchiya S., Fujiwara T., Sato F., Shimada Y., Tanaka E., Sakai Y., Shimizu K., Tsujimoto G. MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J. Biol. Chem. 2011;286:420-428.

    Not in our library10.1074/jbc.m110.170852

  383. 383.

    Qiu J., Zhou X.Y., Zhou X.G., Cheng R., Liu H.Y., Li Y. Neuroprotective effects of microRNA-210 against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells. Mol. Med. Rep. 2013;7:1955-1959.

    Not in our library10.3892/mmr.2013.1431

  384. 384.

    Chio C.C., Lin J.W., Cheng H.A., Chiu W.T., Wang Y.H., Wang J.J., Hsing C.H., Chen R.M. MicroRNA-210 targets antiapoptotic Bcl-2 expression and mediates hypoxia-induced apoptosis of neuroblastoma cells. Arch. Toxicol. 2013;87:459-468.

    Not in our library10.1007/s00204-012-0965-5

  385. 385.

    Crosby M.E., Kulshreshtha R., Ivan M., Glazer P.M. MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 2009;69:1221-1229.

    Not in our library10.1158/0008-5472.can-08-2516

  386. 386.

    Huang X., Ding L., Bennewith K.L., Tong R.T., Welford S.M., Ang K.K., Story M., Le Q.T., Giaccia A.J. Hypoxia-inducible miR-210 regulates normoxic gene expression involved in tumor initiation. Mol. Cell. 2009;35:856-867.

    Not in our library10.1016/j.molcel.2009.09.006

  387. 387.

    Urbich C., Kuehbacher A., Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc. Res. 2008;79:581-588.

    Not in our library10.1093/cvr/cvn156

  388. 388.

    Poliseno L., Tuccoli A., Mariani L., Evangelista M., Citti L., Woods K., Mercatanti A., Hammond S., Rainaldi G. MicroRNAs modulate the angiogenic properties of HUVECs. Blood. 2006;108:3068-3071.

    Not in our library10.1182/blood-2006-01-012369

  389. 389.

    Ye X., Bai W., Zhu H., Zhang X., Chen Y., Wang L., Yang A., Zhao J., Jia L. miR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN. BMB Rep. 2014;47:268-273.

    Not in our library10.5483/bmbrep.2014.47.5.165

  390. 390.

    Garofalo M., Di Leva G., Romano G., Nuovo G., Suh S.S., Ngankeu A., Taccioli C., Pichiorri F., Alder H., Secchiero P., et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16:498-509.

    Not in our library10.1016/j.ccr.2009.10.014

  391. 391.

    Suarez Y., Fernandez-Hernando C., Pober J.S., Sessa W.C. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ. Res. 2007;100:1164-1173.

    Not in our library10.1161/01.res.0000265065.26744.17

  392. 392.

    Cai G., Qiao S., Chen K. Suppression of miR-221 inhibits glioma cells proliferation and invasion via targeting SEMA3B. Biol. Res. 2015;48:37.

    Not in our library10.1186/s40659-015-0030-y

  393. 393.

    Kneitz B., Krebs M., Kalogirou C., Schubert M., Joniau S., van Poppel H., Lerut E., Kneitz S., Scholz C.J., Strobel P., et al. Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3. Cancer Res. 2014;74:2591-2603.

    Not in our library10.1158/0008-5472.can-13-1606

  394. 394.

    Zhong C., Ding S., Xu Y., Huang H. MicroRNA-222 promotes human non-small cell lung cancer H460 growth by targeting p27. Int. J. Clin. Exp. Med. 2015;8:5534-5540.

    Not in our library

  395. 395.

    Yang C.J., Shen W.G., Liu C.J., Chen Y.W., Lu H.H., Tsai M.M., Lin S.C. MiR-221 and miR-222 expression increased the growth and tumorigenesis of oral carcinoma cells. J. Oral Pathol. Med. 2011;40:560-566.

    Not in our library10.1111/j.1600-0714.2010.01005.x

  396. 396.

    Sun T., Wang X., He H.H., Sweeney C.J., Liu S.X., Brown M., Balk S., Lee G.S., Kantoff P.W. miR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A. Oncogene. 2014;33:2790-2800.

    Not in our library10.1038/onc.2013.230

  397. 397.

    Rao X., Di Leva G., Li M., Fang F., Devlin C., Hartman-Frey C., Burow M.E., Ivan M., Croce C.M., Nephew K.P. MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene. 2011;30:1082-1097.

    Not in our library10.1038/onc.2010.487

  398. 398.

    Dentelli P., Traversa M., Rosso A., Togliatto G., Olgasi C., Marchio C., Provero P., Lembo A., Bon G., Annaratone L., et al. miR-221/222 control luminal breast cancer tumor progression by regulating different targets. Cell Cycle. 2014;13:1811-1826.

    Not in our library10.4161/cc.28758

  399. 399.
    MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma · 2010
    No notice
  400. 400.

    Goto Y., Kojima S., Nishikawa R., Kurozumi A., Kato M., Enokida H., Matsushita R., Yamazaki K., Ishida Y., Nakagawa M., et al. MicroRNA expression signature of castration-resistant prostate cancer: The microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker. Br. J. Cancer. 2015;113:1055-1065.

    Not in our library10.1038/bjc.2015.300

  401. 401.

    Ding L., Xu Y., Zhang W., Deng Y., Si M., Du Y., Yao H., Liu X., Ke Y., Si J., et al. miR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res. 2010;20:784-793.

    Not in our library10.1038/cr.2010.79

  402. 402.

    Tsukamoto Y., Nakada C., Noguchi T., Tanigawa M., Nguyen L.T., Uchida T., Hijiya N., Matsuura K., Fujioka T., Seto M., et al. MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. Cancer Res. 2010;70:2339-2349.

    Not in our library10.1158/0008-5472.can-09-2777

  403. 403.

    Song S.D., Zhou J., Zhou J., Zhao H., Cen J.N., Li D.C. MicroRNA-375 targets the 3-phosphoinositide-dependent protein kinase-1 gene in pancreatic carcinoma. Oncol. Lett. 2013;6:953-959.

    Not in our library10.3892/ol.2013.1510

  404. 404.

    Luo J., Wu J., Li Z., Qin H., Wang B., Wong T.S., Yang W., Fu Q.L., Lei W. miR-375 suppresses IGF1R expression and contributes to inhibition of cell progression in laryngeal squamous cell carcinoma. BioMed Res. Int. 2014;2014:374598.

    Not in our library10.1155/2014/374598

  405. 405.

    Mao Q., Quan T., Luo B., Guo X., Liu L., Zheng Q. MiR-375 targets KLF4 and impacts the proliferation of colorectal carcinoma. Tumour Biol. 2015.

    Not in our library10.1007/s13277-015-3809-0

  406. 406.

    Shi W., Yang J., Li S., Shan X., Liu X., Hua H., Zhao C., Feng Z., Cai Z., Zhang L., et al. Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5. Oncotarget. 2015;6:40172-40185.

    Not in our library10.18632/oncotarget.5502

  407. 407.

    Wang X.Z., Hang Y.K., Liu J.B., Hou Y.Q., Wang N., Wang M.J. Over-expression of microRNA-375 inhibits papillary thyroid carcinoma cell proliferation and induces cell apoptosis by targeting ERBB2. J. Pharmacol. Sci. 2016;130:78-84.

    Not in our library10.1016/j.jphs.2015.12.001

  408. 408.

    Shen Z.Y., Zhang Z.Z., Liu H., Zhao E.H., Cao H. miR-375 inhibits the proliferation of gastric cancer cells by repressing ERBB2 expression. Exp. Ther. Med. 2014;7:1757-1761.

    Not in our library10.3892/etm.2014.1627

  409. 409.

    Wang Y., Tang Q., Li M., Jiang S., Wang X. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem. Biophys. Res. Commun. 2014;444:199-204.

    Not in our library10.1016/j.bbrc.2014.01.028

  410. 410.

    He J., Cao Y., Su T., Jiang Y., Jiang L., Zhou W., Zhang C., Wang W., Ning G. Downregulation of miR-375 in aldosterone-producing adenomas promotes tumour cell growth via MTDH. Clin. Endocrinol. (Oxf.). 2015;83:581-589.

    Not in our library10.1111/cen.12814

  411. 411.

    Hudson J., Duncavage E., Tamburrino A., Salerno P., Xi L., Raffeld M., Moley J., Chernock R.D. Overexpression of miR-10a and miR-375 and downregulation of YAP1 in medullary thyroid carcinoma. Exp. Mol. Pathol. 2013;95:62-67.

    Not in our library10.1016/j.yexmp.2013.05.001

  412. 412.

    Jung H.M., Patel R.S., Phillips B.L., Wang H., Cohen D.M., Reinhold W.C., Chang L.J., Yang L.J., Chan E.K. Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA-mRNA interactions. Mol. Biol. Cell. 2013;24:1638-1648.

    Not in our library10.1091/mbc.e12-12-0891

  413. 413.

    He X.X., Chang Y., Meng F.Y., Wang M.Y., Xie Q.H., Tang F., Li P.Y., Song Y.H., Lin J.S. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2012;31:3357-3369.

    Not in our library10.1038/onc.2011.500

  414. 414.

    Zaharie F., Muresan M.S., Petrushev B., Berce C., Gafencu G.A., Selicean S., Jurj A., Cojocneanu-Petric R., Lisencu C.I., Pop L.A., et al. Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer. J. Gastroint. Liver Dis. 2015;24:435-443.

    Not in our library10.15403/jgld.2014.1121.244.375

  415. 415.

    Yoda S., Soejima K., Hamamoto J., Yasuda H., Nakayama S., Satomi R., Terai H., Ikemura S., Sato T., Naoki K., et al. Claudin-1 is a novel target of miR-375 in non-small-cell lung cancer. Lung Cancer. 2014;85:366-372.

    Not in our library10.1016/j.lungcan.2014.06.009

  416. 416.

    Ye X.M., Zhu H.Y., Bai W.D., Wang T., Wang L., Chen Y., Yang A.G., Jia L.T. Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R. BMC Cancer. 2014;14:627.

    Not in our library10.1186/1471-2407-14-134

  417. 417.

    Liu Y., Xing R., Zhang X., Dong W., Zhang J., Yan Z., Li W., Cui J., Lu Y. miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells. DNA Repair. (Amst.). 2013;12:741-750.

    Not in our library10.1016/j.dnarep.2013.06.002

  418. 418.

    Mussnich P., Rosa R., Bianco R., Fusco A., D'Angelo D. miR-199a-5p and miR-375 affect colon cancer cell sensitivity to cetuximab by targeting PHLPP1. Expert Opin. Ther. Targets. 2015;19:1017-1026.

    Not in our library10.1517/14728222.2015.1057569

  419. 419.
    SHOX2 Is a Direct miR-375 Target and a Novel Epithelial-to-Mesenchymal Transition Inducer in Breast Cancer Cells · 2014
    Not checked
  420. 420.

    Chang Y., Yan W., He X., Zhang L., Li C., Huang H., Nace G., Geller D.A., Lin J., Tsung A. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology. 2012;143:177-187.

    Not in our library10.1053/j.gastro.2012.04.009

  421. 421.

    Szigeti A., Tatrai E., Szamosi A., Vargha P., Nagy Z.Z., Nemeth J., DeBuc D.C., Somfai G.M. A morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation. PLoS ONE. 2014;9:627.

    Not in our library10.1371/journal.pone.0088363

  422. 422.

    Park N.J., Zhou X., Yu T., Brinkman B.M., Zimmermann B.G., Palanisamy V., Wong D.T. Characterization of salivary RNA by cDNA library analysis. Arch. Oral Biol. 2007;52:30-35.

    Not in our library10.1016/j.archoralbio.2006.08.014

  423. 423.

    Weber J.A., Baxter D.H., Zhang S., Huang D.Y., Huang K.H., Lee M.J., Galas D.J., Wang K. The microRNA spectrum in 12 body fluids. Clin. Chem. 2010;56:1733-1741.

    Not in our library10.1373/clinchem.2010.147405

  424. 424.

    Liu C.J., Lin S.C., Yang C.C., Cheng H.W., Chang K.W. Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck. 2012;34:219-224.

    Not in our library10.1002/hed.21713

  425. 425.

    Momen-Heravi F., Trachtenberg A.J., Kuo W.P., Cheng Y.S. Genomewide Study of Salivary MicroRNAs for Detection of Oral Cancer. J. Dent. Res. 2014;93:86S-93S.

    Not in our library10.1177/0022034514531018

  426. 426.

    Zahran F., Ghalwash D., Shaker O., Al-Johani K., Scully C. Salivary microRNAs in oral cancer. Oral Dis. 2015;21:739-747.

    Not in our library10.1111/odi.12340

  427. 427.

    Duz M.B., Karatas O.F., Guzel E., Turgut N.F., Yilmaz M., Creighton C.J., Ozen M. Identification of miR-139-5p as a saliva biomarker for tongue squamous cell carcinoma: A pilot study. Cell. Oncol. (Dordr.). 2015.

    Not in our library10.1007/s13402-015-0259-z

  428. 428.

    Matse J.H., Yoshizawa J., Wang X., Elashoff D., Bolscher J.G., Veerman E.C., Bloemena E., Wong D.T. Discovery and prevalidation of salivary extracellular microRNA biomarkers panel for the noninvasive detection of benign and malignant parotid gland tumors. Clin. Cancer Res. 2013;19:3032-3038.

    Not in our library10.1158/1078-0432.ccr-12-3505

  429. 429.

    Xie Z., Yin X., Gong B., Nie W., Wu B., Zhang X., Huang J., Zhang P., Zhou Z., Li Z. Salivary microRNAs show potential as a noninvasive biomarker for detecting resectable pancreatic cancer. Cancer Prev. Res. (Phila). 2015;8:165-173.

    Not in our library10.1158/1940-6207.capr-14-0192

  430. 430.

    Huang X., Liang M., Dittmar R., Wang L. Extracellular microRNAs in urologic malignancies: Chances and challenges. Int. J. Mol. Sci. 2013;14:14785-14799.

    Not in our library10.3390/ijms140714785

  431. 431.

    Zhou J., Gong G., Tan H., Dai F., Zhu X., Chen Y., Wang J., Liu Y., Chen P., Wu X., et al. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma. Oncol. Rep. 2015;33:2915-2923.

    Not in our library10.3892/or.2015.3937

  432. 432.

    Abdalla M.A., Haj-Ahmad Y. Promising Candidate Urinary MicroRNA Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients. J. Cancer. 2012;3:19-31.

    Not in our library10.7150/jca.3.19

  433. 433.

    Machida A., Ohkubo T., Yokota T. Circulating microRNAs in the cerebrospinal fluid of patients with brain diseases. Methods Mol. Biol. 2013;1024:203-209.

    Not in our library10.1007/978-1-62703-453-1_16

  434. 434.

    Baraniskin A., Kuhnhenn J., Schlegel U., Chan A., Deckert M., Gold R., Maghnouj A., Zollner H., Reinacher-Schick A., Schmiegel W., et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood. 2011;117:3140-3146.

    Not in our library10.1182/blood-2010-09-308684

  435. 435.

    Baraniskin A., Kuhnhenn J., Schlegel U., Maghnouj A., Zollner H., Schmiegel W., Hahn S., Schroers R. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol. 2012;14:29-33.

    Not in our library10.1093/neuonc/nor169

  436. 436.

    Baraniskin A., Kuhnhenn J., Schlegel U., Schmiegel W., Hahn S., Schroers R. MicroRNAs in cerebrospinal fluid as biomarker for disease course monitoring in primary central nervous system lymphoma. J. Neurooncol. 2012;109:239-244.

    Not in our library10.1007/s11060-012-0908-2

  437. 437.

    Tuo J., Shen D., Yang H.H., Chan C.C. Distinct microRNA-155 expression in the vitreous of patients with primary vitreoretinal lymphoma and uveitis. Am. J. Ophthalmol. 2014;157:728-734.

    Not in our library10.1016/j.ajo.2013.12.014

  438. 438.

    Ragusa M., Caltabiano R., Russo A., Puzzo L., Avitabile T., Longo A., Toro M.D., di Pietro C., Purrello M., Reibaldi M. MicroRNAs in vitreus humor from patients with ocular diseases. Mol. Vis. 2013;19:430-440.

    Not in our library

  439. 439.

    Gu Y.Q., Gong G., Xu Z.L., Wang L.Y., Fang M.L., Zhou H., Xing H., Wang K.R., Sun L. miRNA profiling reveals a potential role of milk stasis in breast carcinogenesis. Int. J. Mol. Med. 2014;33:1243-1249.

    Not in our library10.3892/ijmm.2014.1677

  440. 440.

    Selth L.A., Roberts M.J., Chow C.W., Marshall V.R., Doi S.A., Vincent A.D., Butler L.M., Lavin M.F., Tilley W.D., Gardiner R.A. Human seminal fluid as a source of prostate cancer-specific microRNA biomarkers. Endocr. Relat. Cancer. 2014;21:L17-L21.

    Not in our library10.1530/erc-14-0234

  441. 441.

    Margue C., Reinsbach S., Philippidou D., Beaume N., Walters C., Schneider J.G., Nashan D., Behrmann I., Kreis S. Comparison of a healthy miRNome with melanoma patient miRNomes: Are microRNAs suitable serum biomarkers for cancer? Oncotarget. 2015;6:12110-12127.

    Not in our library10.18632/oncotarget.3661

  442. 442.
    Standardization of sample collection, isolation and analysis methods in extracellular vesicle research · 2013
    No notice
  443. 443.

    McDonald J.S., Milosevic D., Reddi H.V., Grebe S.K., Algeciras-Schimnich A. Analysis of circulating microRNA: Preanalytical and analytical challenges. Clin. Chem. 2011;57:833-840.

    Not in our library10.1373/clinchem.2010.157198

  444. 444.
    Haemolysis during Sample Preparation Alters microRNA Content of Plasma · 2011
    No notice
  445. 445.

    Pritchard C.C., Kroh E., Wood B., Arroyo J.D., Dougherty K.J., Miyaji M.M., Tait J.F., Tewari M. Blood cell origin of circulating microRNAs: A cautionary note for cancer biomarker studies. Cancer Prev. Res. (Phila). 2012;5:492-497.

    Not in our library10.1158/1940-6207.capr-11-0370

  446. 446.

    Kannan M., Atreya C. Differential profiling of human red blood cells during storage for 52 selected microRNAs. Transfusion. 2010;50:1581-1588.

    Not in our library10.1111/j.1537-2995.2010.02585.x

  447. 447.

    Al-Soud W.A., Radstrom P. Purification and characterization of PCR-inhibitory components in blood cells. J. Clin. Microbiol. 2001;39:485-493.

    Not in our library10.1128/jcm.39.2.485-493.2001

  448. 448.

    Heneghan H.M., Miller N., Kerin M.J. Circulating miRNA signatures: Promising prognostic tools for cancer. J. Clin. Oncol. 2010;28:e573-e574.

    Not in our library10.1200/jco.2010.29.8901

  449. 449.

    Gourzones C., Ferrand F.R., Amiel C., Verillaud B., Barat A., Guerin M., Gattolliat C.H., Gelin A., Klibi J., Chaaben A.B., et al. Consistent high concentration of the viral microRNA BART17 in plasma samples from nasopharyngeal carcinoma patients—Evidence of non-exosomal transport. Virol. J. 2013;10:119.

    Not in our library10.1186/1743-422x-10-119

  450. 450.

    Hu J., Wang Z., Tan C.J., Liao B.Y., Zhang X., Xu M., Dai Z., Qiu S.J., Huang X.W., Sun J., et al. Plasma microRNA, a potential biomarker for acute rejection after liver transplantation. Transplantation. 2013;95:991-999.

    Not in our library10.1097/tp.0b013e31828618d8

  451. 451.
    Plasma Processing Conditions Substantially Influence Circulating microRNA Biomarker Levels · 2013
    No notice
  452. 452.

    Kim Y.K., Yeo J., Kim B., Ha M., Kim V.N. Short structured RNAs with low GC content are selectively lost during extraction from a small number of cells. Mol. Cell. 2012;46:893-895.

    Not in our library10.1016/j.molcel.2012.05.036

  453. 453.

    Whitney A.R., Diehn M., Popper S.J., Alizadeh A.A., Boldrick J.C., Relman D.A., Brown P.O. Individuality and variation in gene expression patterns in human blood. Proc. Natl. Acad. Sci. USA. 2003;100:1896-1901.

    Not in our library10.1073/pnas.252784499

  454. 454.

    Watson A.K., Witwer K.W. Do platform-specific factors explain microRNA profiling disparities? Clin. Chem. 2012;58:472-474.

    Not in our library10.1373/clinchem.2011.175281

  455. 455.

    Dickinson B., Zhang Y., Petrick J.S., Heck G., Ivashuta S., Marshall W.S. Lack of detectable oral bioavailability of plant microRNAs after feeding in mice. Nat. Biotechnol. 2013;31:965-967.

    Not in our library10.1038/nbt.2737

  456. 456.
    A Critical Evaluation of microRNA Biomarkers in Non-Neoplastic Disease · 2014
    No notice
  457. 457.

    Xiang M., Zeng Y., Yang R., Xu H., Chen Z., Zhong J., Xie H., Xu Y., Zeng X. U6 is not a suitable endogenous control for the quantification of circulating microRNAs. Biochem. Biophys. Res. Commun. 2014;454:210-214.

    Not in our library10.1016/j.bbrc.2014.10.064

  458. 458.
    Identification and validation of miRNAs as endogenous controls for RQ-PCR in blood specimens for breast cancer studies. · 2013
    Not checked
  459. 459.
    Comprehensive microRNA Analysis Identifies miR-24 and miR-125a-5p as Plasma Biomarkers for Rheumatoid Arthritis · 2013
    No notice

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