miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice

Hepatology. 2010 Dec;52(6):2148-57. doi: 10.1002/hep.23915. Epub 2010 Oct 26.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by interacting with the 3' untranslated region (3'-UTR) of multiple mRNAs. Recent studies have linked miRNAs to the development of cancer metastasis. In this study, we show that miR-194 is specifically expressed in the human gastrointestinal tract and kidney. Moreover, miR-194 is highly expressed in hepatic epithelial cells, but not in Kupffer cells or hepatic stellate cells, two types of mesenchymal cells in the liver. miR-194 expression was decreased in hepatocytes cultured in vitro, which had undergone a dedifferentiation process. Furthermore, expression of miR-194 was low in liver mesenchymal-like cancer cell lines. The overexpression of miR-194 in liver mesenchymal-like cancer cells reduced the expression of the mesenchymal cell marker N-cadherin and suppressed invasion and migration of the mesenchymal-like cancer cells both in vitro and in vivo. We further demonstrated that miR-194 targeted the 3'-UTRs of several genes that were involved in epithelial-mesenchymal transition and cancer metastasis.

Conclusion: These results support a role of miR-194, which is specifically expressed in liver parenchymal cells, in preventing liver cancer cell metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / pathology*
  • Lung Neoplasms / secondary
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / physiology*
  • Neoplasm Metastasis / prevention & control*

Substances

  • MIRN194 microRNA, human
  • MIRN194 microRNA, mouse
  • MicroRNAs