miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice

Authors

  • Zhipeng Meng,

    1. Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
    2. Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
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    • These authors contributed equally to this work.

  • Xianghui Fu,

    1. Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
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    • These authors contributed equally to this work.

  • Xiaosong Chen,

    1. Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
    2. Department of Plastic Surgery, Union Hospital of Fujian Medical University, Fuzhou, China
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  • Samuel Zeng,

    1. Eugene and Ruth Roberts Summer Student Program, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
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  • Yan Tian,

    1. Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
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  • Richard Jove,

    1. Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
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  • Rongzhen Xu,

    1. Cancer Institute, Second Affiliated Hospital, School of Medicine of Zhejiang University, Hangzhou, China
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  • Wendong Huang

    Corresponding author
    1. Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
    2. Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
    • Division of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010
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  • Potential conflict of interest: Nothing to report.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by interacting with the 3′ untranslated region (3′-UTR) of multiple mRNAs. Recent studies have linked miRNAs to the development of cancer metastasis. In this study, we show that miR-194 is specifically expressed in the human gastrointestinal tract and kidney. Moreover, miR-194 is highly expressed in hepatic epithelial cells, but not in Kupffer cells or hepatic stellate cells, two types of mesenchymal cells in the liver. miR-194 expression was decreased in hepatocytes cultured in vitro, which had undergone a dedifferentiation process. Furthermore, expression of miR-194 was low in liver mesenchymal-like cancer cell lines. The overexpression of miR-194 in liver mesenchymal-like cancer cells reduced the expression of the mesenchymal cell marker N-cadherin and suppressed invasion and migration of the mesenchymal-like cancer cells both in vitro and in vivo. We further demonstrated that miR-194 targeted the 3′-UTRs of several genes that were involved in epithelial-mesenchymal transition and cancer metastasis. Conclusion: These results support a role of miR-194, which is specifically expressed in liver parenchymal cells, in preventing liver cancer cell metastasis. (HEPATOLOGY 2010;.)

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