MicroRNA-125b Suppressesed Human Liver Cancer... : Hepatology (original) (raw)

Hepatobiliary Malignancies

MicroRNA-125b Suppressesed Human Liver Cancer Cell Proliferation and Metastasis by Directly Targeting Oncogene LIN28B

Hepatology

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5

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1731

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1740

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November 2010

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| DOI: 10.1002/hep.23904

MicroRNAs (miRNAs) are small, noncoding RNAs that can act as oncogenes or tumor suppressors in human cancer. Our previous study showed that miR-125b was a prognostic indicator for patients with hepatocellular carcinoma (HCC), but its functions and exact mechanisms in hepatic carcinogenesis are still unknown. Here we demonstrate that miR-125b suppressed HCC cell growth in vitro and in vivo . Moreover, miR-125b increased p21Cip1/Waf1 expression and arrested cell cycle at G1 to S transition. In addition, miR-125b inhibited HCC cell migration and invasion. Further studies revealed that LIN28B was a downstream target of miR-125b in HCC cells as miR-125b bound directly to the 3′ untranslated region of LIN28B , thus reducing both the messenger RNA and protein levels of LIN28B . Silencing of LIN28B recapitulated the effects of miR-125b overexpression, whereas enforced expression of LIN28B reversed the suppressive effects of miR-125b.

Conclusion:

These findings indicate that miR-125b exerts tumor-suppressive effects in hepatic carcinogenesis through the suppression of oncogene LIN28B expression and suggest a therapeutic application of miR-125b in HCC. (Hepatology 2010)

Copyright © 2010 American Association for the Study of Liver Diseases.