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Direct targeting of HGF by miR-16 regulates proliferation and migration in gastric cancer

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Tumor Biology

Abstract

MicroRNAs (miRNAs) have been reported to be involved in each stage of tumor development in various types of cancers. We have previously showed that miR-16 is downregulated in cancer and acts as a tumor suppressor. Other studies indicated that hepatocyte growth factor (HGF)/c-Met is implicated in proliferation, migration, and other pathophysiological processes. However, little is known about the relationship between miR-16 and HGF/c-Met in gastric cancer (GC). In the present study, we used bioinformatics tools and related experiments to search for miRNAs targeting HGF. Here, we found that miR-16 suppressed HGF protein expression by directly targeting 3′-untranslated region (UTR) of HGF mRNA. Subsequently, it was illustrated the downregulation of miR-16 promotes, while overexpressed of miR-16 significantly inhibits cell proliferation and migration by negatively regulating HGF/c-Met pathway. Moreover, the biological role of HGF in GC cells was determined by using HGF siRNA and HGF-overexpressing plasmid, respectively. To conclude, our results provide a potential target by using miR-16 for the future clinical treatment of GC.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81372394) and Tianjin Health and Family Planning Commission Foundation of Science and Technology (15KG142). This work was also supported by grants from National Research Platform of Clinical Evaluation Technology for New Anticancer Drugs (No. 2013ZX09303001). The funders had no role in study design; in collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit this article for publication.

Author contributions

Shuang Li, Haiyang Zhang, Xinyi Wang, Yanjun Qu, and Jingjing Duan performed most of the experiments, analyzed data, and wrote the manuscript. Ting Deng, Rui Liu, Tao Ning, and Le Zhang reviewed and edited the manuscript. Ming Bai and Likun Zhou performed some experiments. Yi Ba and Guoguang Ying designed the experiments and edited the manuscript. Yi Ba is the guarantor of this work, has full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huan Hu Xi Road 18, Tianjin, 300060, China

    Shuang Li, Haiyang Zhang, Xinyi Wang, Yanjun Qu, Jingjing Duan, Rui Liu, Ting Deng, Tao Ning, Le Zhang, Ming Bai, Likun Zhou, Xia Wang, Shaohua Ge, Guoguang Ying & Yi Ba

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  1. Shuang Li
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Correspondence to Guoguang Ying or Yi Ba.

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The study was conducted with the approval of the Ethics Committee of Tianjin Medical University Cancer Institute and Hospital and informed consent was obtained before surgery.

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Shuang Li, Haiyang Zhang, Xinyi Wang, Yanjun Qu, and Jingjing Duan contribute to this work equally.

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Li, S., Zhang, H., Wang, X. et al. Direct targeting of HGF by miR-16 regulates proliferation and migration in gastric cancer. Tumor Biol. 37, 15175–15183 (2016). https://doi.org/10.1007/s13277-016-5390-6

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