MiR-660-5p promotes the progression of hepatocellular carcinoma by interaction with YWHAH via PI3K/Akt signaling pathway

Biochem Biophys Res Commun. 2020 Oct 22;531(4):480-489. doi: 10.1016/j.bbrc.2020.07.034. Epub 2020 Aug 14.

Abstract

Currently, more and more studies show that aberrantly expressed microRNAs (miRNAs) are important driving factors for the pathogenesis of hepatocellular carcinoma (HCC). Based on the TCGA and GEO databases, miR-660-5p was identified as a possible target for HCC in this study.In HCC tissues, miR-660-5pexpressionwasparticularly high, and this was confirmed inHCC cell lines. The upregulatedmiR-660-5p showed correlations with tumor size, tumor number, TNM stage and histological grade. In vitro experimental data, aswellas in vivo evidence showed that miR-660-5p has the ability to significantly enhance the cell proliferation rate, clone formation, migration, invasion, and tumorigenic capacity of HCC cells. YWHAH is validated that targeted by miR-660-5p using dual luciferase reporter assay. Knockdown of YWHAH has been shown to partially reverse the tumor suppressive function of miR-660-5p inhibitor. Furthermore, miR-660-5p/YWHAH axis could activate PI3K/AKT pathway, which promoted EMT and cell cycle processes. In conclusion, this study illustrated the function of miR-660-5p/YWHAH axis in HCC and provided potential targets for treating HCC.

Keywords: Hepatocellular carcinoma; Invasion; PI3K/Akt; Proliferation; miR-660-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / genetics*
  • 14-3-3 Proteins / metabolism
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays

Substances

  • 14-3-3 Proteins
  • MIRN660 microRNA, human
  • MicroRNAs
  • YWHAH protein, human