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MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway

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Summary

MicroRNAs are involved in each stage of tumor development. Activation of the hepatocyte growth factor (HGF)/c-Met axis facilitates the proliferation and migration of cancer cells, and the HGF/c-MET pathway provides potential targets for anticancer treatment. However, the interaction between HGF and miRNAs in hepatocellular carcinoma (HCC) remains unknown. Previous studies have shown that miR-101 is downregulated in various types of cancer and acts as a tumor suppressor, but the role of miR-101 in HCC has not yet been well defined. Here, we show that HGF is upregulated while microRNA-101-3p is significantly downregulated in the tumor tissues of HCC. By combining bioinformatics analysis and luciferase reporter assays, we demonstrated that HGF is a direct target of miR-101. In vitro experiments indicated that miR-101 inhibits the migration and proliferation of HCC cells by targeting the HGF/c-MET axis, and in vivo studies showed that overexpressed miR-101 dramatically suppresses tumor growth. Therefore, the present study identifies miR-101 as a negative regulator of HGF/c-MET and suggests that miRNAs can be used as targeted drugs for the clinical treatment of HCC.

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Funding

This study was supporting by Hunan Natural Science Youth Fund Project (Project number:2018JJ3784. Project name:Molecular mechanism of miR-1181 involvement in promoting proliferation and survival of hepatocellular). The funder had no role in study design; collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit this article for publication.

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Authors and Affiliations

  1. Department of Pathology, Infectious Diseases Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    Yang Liu, Juan Tan & Limin Chen

  2. Medical Oncology Institute, Hunan Cancer Hospital, Changsha, Hunan, China

    Shuangyan Ou

  3. Hunan Polytechnic of Environment and Biology, Hengyang, Hunan, China

    Jun Chen

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  1. Yang Liu
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Correspondence to Limin Chen.

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Yang Liu declares that she has no conflict of interest. Juan Tan declares that she has no conflict of interest. Shuangyan Ou declares that she has no conflict of interest. Jun Chen declares that he has no conflict of interest. Limin Chen declares that she has no conflict of interest.

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All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Liu, Y., Tan, J., Ou, S. et al. MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway. Invest New Drugs 38, 60–69 (2020). https://doi.org/10.1007/s10637-019-00766-8

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  • DOI: https://doi.org/10.1007/s10637-019-00766-8

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