miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization

Abstract

Background Tumor microenvironment (TME) is a complex environment containing tumor cells, tumor-associated macrophages (TAMs), interstitial cells, and non-cellular components. Epithelial–mesenchymal transition (EMT), as a major actor in cancer tumorigenicity and metastasis, was involved in the interaction between TAMs and tumor cells. However, the potential mechanisms of EMT and how EMT-programmed tumor cells affect M2-like TAMs still need further exploration. Methods An integrated analysis of nine CRC miRNA expression datasets was performed. Functional assays, including the EdU, clone formation, wound healing, and transwell assays, were used to determine the anticancer role of miR-195-5p in human CRC progression. Furthermore, RNA immunoprecipitation, RNA decay, and dual-luciferase reporter assays were used to determine the mechanism of miR-195-p CRC progression. Then co-culture, migration, and ELISA assays were applied to determine the role of miR-195-5p in macrophage recruitment and alternative polarization. Xenograft mouse models were used to determine the role of miR-195-5p in CRC tumorigenicity and TAM polarization in vivo. Results An integrated analysis confirmed that miR-195-5p was significantly downregulated in CRC tissues, and patients with a low level of miR-195-5p had significantly shortened overall survival as revealed by the TCGA-COAD dataset. Altered miR-195-5p in colon cancer cells led to distinct changes of proliferation, migration, invasion, and EMT. Mechanistically, miR-195-5p regulated NOTCH2 expression in a post-transcriptional manner by directly binding to 3′-UTR of the Notch2 mRNA. Subsequently, miR-195-5p/NOTCH2 suppressed GATA3-mediated IL-4 secretion in CRC cells and ultimately inhibited M2-like TAM polarization. Conclusions miR-195-5p may play a vital role in regulating NOTCH2-mediated tumor cell EMT, thereby affecting IL-4-related M2-like TAM polarization in CRC.

Full text

We don’t show the text of a retracted or withdrawn paper. The record stays, so citations to it can be checked.

Cited by papers we hold 8

• Decoding the spatiotemporal heterogeneity of tumor-associated macrophages · 2024
  No notice
• MiRNA-mediated EMT and CSCs in cancer chemoresistance · 2021
  Not checked
• EMT‐cancer cells‐derived exosomal miR‐27b‐3p promotes circulating tumour cells‐mediated metastasis by modulating vascular permeability in colorectal cancer · 2021
  No notice
• Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now? · 2021
  No notice
• Non-coding RNAs regulation of macrophage polarization in cancer · 2021
  No notice
• The Role of Interleukins in Colorectal Cancer · 2020
  No notice
• Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression · 2020
  No notice
• Emerging role of tumor cell plasticity in modifying therapeutic response · 2020
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.