CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7

Abstract

Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2.75, 95% confidence interval [CI] 1.74–6.51, p = 0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR-7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.

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Cited by papers we hold 30

• Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks · 2024
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• CircRNAs in colorectal cancer: potential biomarkers and therapeutic targets · 2023
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• The N6-methyladenosine modification of circALG1 promotes the metastasis of colorectal cancer mediated by the miR-342-5p/PGF signalling pathway · 2022
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• PIK3CA mutations-mediated downregulation of circLHFPL2 inhibits colorectal cancer progression via upregulating PTEN · 2022
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• Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p · 2022
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• The role of lncRNA-mediated ceRNA regulatory networks in pancreatic cancer · 2022
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• METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis · 2022
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• Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer · 2021
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• Osteosarcoma and Metastasis · 2021
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• A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer · 2020
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• Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway · 2020
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• Circular RNA-protein interactions: functions, mechanisms, and identification · 2020
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• Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1 · 2020
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• CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer · 2020
  Corrected
• The emerging roles and functions of circular RNAs and their generation · 2019
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• The novel roles of circRNAs in human cancer · 2019
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• Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers · 2019
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• Emerging roles of circRNA in formation and progression of cancer · 2019
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• Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis · 2019
  Corrected
• Circular RNA hsa_circ_001783 regulates breast cancer progression via sponging miR-200c-3p · 2019
  No notice

and 10 more

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