MicroRNA-361-5p suppresses the tumorigenesis of hepatocellular carcinoma through targeting WT1 and suppressing WNT/β-cadherin pathway

Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8823-8832. doi: 10.26355/eurrev_201910_19277.

Abstract

Objective: MicroRNA-361-5p (miR-361-5p) has been found to be involved in the pathogenesis of several human cancers. However, the specific role of miR-361-5p is still unclear in hepatocellular carcinoma (HCC). Therefore, this study was designed to elucidate the function of miR-361-5p in HCC.

Patients and methods: The expression levels of miR-361-5p and Wilms' tumor-1 (WT1) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Moreover, the function of miR-361-5p was examined through Cell Counting Kit-8 (CCK-8) and transwell assays. The protein expressions were examined via Western blot analysis and immunocytochemical assay. Tumor growth of HCC was observed via xenograft tumor formation assay. The relationship between miR-361-5p and WT1 was verified by the Dual-Luciferase assay.

Results: Downregulation of miR-361-5p was identified in HCC, which predicted a worse prognosis in HCC patients. Furthermore, it was found that miR-361-5p suppressed cell proliferation, migration, and invasion in HCC by inhibiting WT1. MiR-361-5p also inhibited tumor growth of HCC. Besides that, miR-361-5p suppressed EMT and negatively activated the WNT/β-cadherin pathway in HCC.

Conclusions: MiR-361-5p suppressed tumorigenesis of HCC by targeting WT1 and inactivating the WNT/β-cadherin pathway.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / metabolism
  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Survival Rate
  • WT1 Proteins / chemistry
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism*
  • Wnt Signaling Pathway
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Cadherins
  • MIRN361 microRNA, human
  • MicroRNAs
  • WT1 Proteins
  • WT1 protein, human