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miR-202 Suppresses Hepatocellular Carcinoma Progression via Downregulating BCL2 Expression
Donghai Zhuang1, Li Liang1, Hongzhan Zhang1
1Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong UniversityJinanP.R. China.
Abstract:
miRNAs play an important role in progression of hepatocellular carcinoma (HCC). In this work, we assessed the function of miR-202 in human HCC and identified BCL2 as its target. We found miR-202 expression was found significantly downregulated, while BCL2 expression was markedly upregulated in HCC tissues and cell lines (HepG2, Hep3B, and HCCLM3). Both miR-202 and BCL2 were closely correlated with major vascular invasion and advanced TNM stage as well as overall survival of HCC patients. Overexpression of miR-202 significantly inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G0/G1 phase, and prevented tumor formation in a xenograft nude mouse model. Further, miR-202 dramatically inhibited migration, invasion, and epithelialmesenchymal transition. miR-202 bound to the 3-untranslated region (3-UTR) of BCL2 mRNA and downregulated the expression level of BCL2 protein. Exogenous BCL2 overexpression weakened the inhibitory effects of miR-202, while inhibition of BCL2 enhanced the inhibitory effects of miR-202. In conclusion, miR-202 serves as a tumor suppressor in HCC progression by downregulating BCL2 expression, indicating miR-202 might be a potential target for HCC.
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