MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2

Hepatology. 2010 Nov;52(5):1731-40. doi: 10.1002/hep.23904.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cell Movement / drug effects
  • Colony-Forming Units Assay
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / drug effects*
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / pharmacology*
  • Polymerase Chain Reaction
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • DNA-Binding Proteins
  • LIN28B protein, human
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins