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MicroRNA-32 Regulates Development and Progression of Hepatocellular Carcinoma by Targeting ADAMTS9 and Affects Its Prognosis

Shengmian Li, Tingting Li, Xiaoming Li, Yue Yao, Xiaojia Jiang, Lianmei Zhao, Wei Guo

Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)

Med Sci Monit Basic Res 2018; 24:177-187

DOI: 10.12659/MSMBR.910522

Available online: 2018-11-05

Published: 2018-11-05


BACKGROUND: MicroRNA-32 (miR-32) induces cell proliferation and metastasis in hepatocellular carcinoma (HCC), but the detailed mechanisms of miR-32 in regulating oncogenesis and development of HCC have not been clarified. The aim of this study was to investigate the effects of miR-32 on HCC and its clinical pathological significance, as well as to determine the functional connection between miR-32 and ADAMTS9 in HCC.
MATERIAL AND METHODS: Quantitative RT-PCR was used to assess the expression levels of miR-32 in HCC tissues, adjacent non-cancerous tissues, and liver cancer cell lines. In vitro cell proliferation, migration, and invasion assays were performed to confirm the biological functions of miR-32. Quantitative RT-PCR, Western blot analysis, and luciferase reporter assays were used to evaluate the role of miR-32 in the regulation of ADAMTS9.
RESULTS: miR-32 was highly expressed in HCC tissues compared with corresponding adjacent non-cancerous tissues. Over-expression of miR-32 was also found in 3 human liver cancer cell lines: SMMC-7721, Huh7, and HepG2. Moreover, increasing expression of miR-32 in HCC tissues was related to shorter overall survival. In vitro over-expression of miR-32 promoted cell proliferation, migration, and invasion; however, the under-expression of miR-32 revealed the opposite effects. Dual-luciferase reporter assay indicated that miR-32 can directly bind to the 3’-UTR of ADAMTS9. Western blot analysis showed that over-expression of miR-32 decreased expression of ADAMTS9 protein. Rescue tests further verified the connection between miR-32 and ADAMTS9.
CONCLUSIONS: Our data indicate that miR-32 accelerates progression in HCC by targeting ADAMTS9, and the abnormal expression of miR-32 is correlated with prognosis and could become a potential therapeutic target.

Keywords: ADAM Proteins, Prognosis