Downregulation of miR-7 upregulates Cullin 5 (CUL5) to facilitate G1/S transition in human hepatocellular carcinoma cells

IUBMB Life. 2013 Dec;65(12):1026-34. doi: 10.1002/iub.1231. Epub 2013 Dec 13.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that participate in the regulation of gene expression. In this study, we demonstrate that miR-7 was downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent non-tumor tissue. Over-expression of miR-7 in QGY-7703 and HepG2 cell lines inhibited colony formation and induced G1/S phase arrest, whereas knockdown of miR-7 produced the opposite phenotype. A tumor suppressor gene, CUL5, was identified as a direct target of miR-7, and CUL-5 is upregulated upon the binding of miR-7 to its 3'UTR. Furthermore, suppression of CUL5 also suppressed cell colony formation and induced cell cycle arrest. Ectopic expression of CUL5 abrogated the effects of miR-7 inhibition on QGY-7703 and HepG2 cell lines. These results indicate that miR-7 suppresses colony formation and causes cell cycle arrest via upregulation of CUL5, and it may function as a tumor suppressor in HCC.

Keywords: CUL5; cell cycle; hepatocellular carcinoma; miR-7; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Proliferation
  • Cullin Proteins / genetics*
  • Cullin Proteins / metabolism
  • Down-Regulation
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA Interference

Substances

  • 3' Untranslated Regions
  • CUL5 protein, human
  • Cullin Proteins
  • MIRN7 microRNA, human
  • MicroRNAs