miR-181b promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients

Biochem Biophys Res Commun. 2012 Apr 27;421(1):4-8. doi: 10.1016/j.bbrc.2012.03.025. Epub 2012 Mar 13.

Abstract

MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because of the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-β1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-β1 pathway by a currently unknown mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation*
  • Cyclin-Dependent Kinase Inhibitor p27 / blood
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology

Substances

  • MIrn181 microRNA, human
  • MicroRNAs
  • Transforming Growth Factor beta
  • Cyclin-Dependent Kinase Inhibitor p27