miR-198 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the HGF/c-MET pathway

FEBS Lett. 2011 Jul 21;585(14):2229-34. doi: 10.1016/j.febslet.2011.05.042. Epub 2011 Jun 7.

Abstract

Metastasis is the leading cause of death in patients with hepatocellular carcinoma (HCC) and microRNAs have been implicated to influence this process. Emerging evidence indicates that miR-198 is down-regulated in HCC compared to normal liver parenchyma, but the functional roles of miR-198 in HCC cells remains unexplored. Herein, we show that miR-198 directly targets c-MET via its 3'UTR. Forced expression of miR-198 decreased c-MET expression at both mRNA and protein levels and consequently diminished HGF induced phosphorylation of p44/42 MAPK in HCC cells. Forced expression of miR-198 inhibited HGF promotion of HCC cell migration and invasion in a c-MET dependent manner. In conclusion, we have identified miR-198 as a novel suppressor of HCC cell invasion by negative regulation of the HGF/c-MET pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction / physiology

Substances

  • 3' Untranslated Regions
  • MIRN198 microRNA, human
  • MicroRNAs
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3