Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82

Biochem Biophys Res Commun. 2014 Apr 4;446(2):541-8. doi: 10.1016/j.bbrc.2014.03.006. Epub 2014 Mar 12.

Abstract

Aim: To investigate the metastatic effects and mechanisms of miR-197 in hepatocellular carcinoma (HCC).

Methods and results: The levels of miR-197 increased in HCC cells and tissues compared with a normal hepatic cell line (LO2) and adjacent nontumorous liver tissues, respectively. miR-197 expression negatively correlated with CD82 mRNA expression in these cell lines and tissues. Dual luciferase reporter assay and Western blot confirmed a direct interaction between miR-197 and CD82 3'UTR sequences. After miR-197 was silenced in HCC cells, CD82 expression increased. In the presence of human hepatocyte growth factor (HGF), cells silenced for anti-miR-197 exhibited elongated cellular tails and diminished lamellipodia due to reductions in both ROCK activity and the levels of Rac 1 protein. Downregulation of miR-197 along with the upregulation of CD82 in HCC cells resulted in the inhibition of HCC migration and invasion in vitro and in vivo.

Conclusion: Taken together, these data suggest that anti-miR-197 suppresses HCC migration and invasion by targeting CD82. The regulation of the miR-197/CD82 axis could be a novel therapeutic target in future HCC effective therapy.

Keywords: CD82; Hepatocellular carcinoma; Metastasis; miR-197.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / physiopathology*
  • Cell Movement / genetics
  • Gene Silencing*
  • Gene Targeting / methods*
  • Humans
  • Kangai-1 Protein / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Tumor Cells, Cultured

Substances

  • CD82 protein, human
  • Kangai-1 Protein
  • MIRN197 microRNA, human
  • MicroRNAs