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

AbstractUNLABELLED:
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.
AuthorsLinhui Liang, Chun-Ming Wong, Qiao Ying, Dorothy Ngo-Yin Fan, Shenglin Huang, Jie Ding, Jian Yao, Mingxia Yan, Jinjun Li, Ming Yao, Irene Oi-Lin Ng, Xianghuo He
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 52 Issue 5 Pg. 1731-40 (Nov 2010) ISSN: 1527-3350 [Electronic] United States
PMID20827722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • LIN28B protein, human
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
Topics
  • Cell Cycle (drug effects)
  • Cell Division (drug effects)
  • Cell Movement (drug effects)
  • Colony-Forming Units Assay
  • DNA-Binding Proteins (antagonists & inhibitors, drug effects)
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Liver Neoplasms (genetics, pathology)
  • MicroRNAs (genetics, pharmacology)
  • Polymerase Chain Reaction
  • RNA, Messenger (drug effects, genetics)
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

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