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

Authors

  • Linhui Liang,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Chun-Ming Wong,

    1. State Key Laboratory for Liver Research, Department of Pathology, the University of Hong Kong, Hong Kong, China
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  • Qiao Ying,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Dorothy Ngo-Yin Fan,

    1. State Key Laboratory for Liver Research, Department of Pathology, the University of Hong Kong, Hong Kong, China
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  • Shenglin Huang,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jie Ding,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jian Yao,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Mingxia Yan,

    1. Department of Experimental Pathology, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jinjun Li,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Ming Yao,

    1. Department of Experimental Pathology, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Irene Oi-Lin Ng,

    1. State Key Laboratory for Liver Research, Department of Pathology, the University of Hong Kong, Hong Kong, China
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  • Xianghuo He

    Corresponding author
    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    • State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, No.25/Ln.2200, Xie Tu Road, Shanghai 200032, China
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      fax: (86)-21-64436539


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    Potential conflict of interest: Nothing to report.

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. (HEPATOLOGY 2010)

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