4.5 Article

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

Journal

FEBS LETTERS
Volume 585, Issue 14, Pages 2229-2234

Publisher

WILEY
DOI: 10.1016/j.febslet.2011.05.042

Keywords

miR-198; c-MET; Hepatocellular carcinoma; Invasion

Funding

  1. National Key Scientific Program of China [2010CB912804, 2007CB914801, 2011CBA01103]
  2. National Natural Science Foundation of China [30971492, 090413090]
  3. Fundamental Research Funds for the Central Universities [WK2070000008]
  4. CAS [2010T2S03]

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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. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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