MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma

Chem Biol Drug Des. 2022 Aug;100(2):280-289. doi: 10.1111/cbdd.14063. Epub 2022 May 30.

Abstract

Micro-RNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC) as potential therapeutic targets for HCC. In this study, we found that miR-27a-3p was highly expressed in HCC, which was associated with lower survival rates of HCC patients. In vivo and in vitro functional experiments confirmed that over-expression or knock-down miR-27a-3p could significantly affect the proliferation ability of HCCLM3 and Huh-7, two HCC cell lines. Ubiquitin-specific protease 46 (USP46) was confirmed as the key target gene of miR-27a-3p in HCC via RNA-seq, quantitative polymerase chain reaction, Western blotting, and luciferase report. When knocking down USP46, the proliferation activity of HCC cells was significantly enhanced, while it was significantly inhibited after over-expressing USP4. Above results suggest that the abnormally over-expressed miR-27a-3p in liver promotes the proliferation of cancer cells and accelerates the development of HCC by targeting inhibition the expression of USP46. Targeting miR-27a-3p may be an effective strategy for prevention and treatment of HCC.

Keywords: MiR-27a-3p; USP46; cell proliferation; hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Endopeptidases
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism

Substances

  • MIRN27 microRNA, human
  • MicroRNAs
  • USP4 protein, human
  • Endopeptidases
  • ubiquitin-specific peptidase 46, human
  • Ubiquitin-Specific Proteases