MiRNA-1179 suppresses the metastasis of hepatocellular carcinoma by interacting with ZEB2

H.-B. Gao, F.-Z. Gao, X.-F. Chen

Department of Infectious Diseases, Binzhou People’s Hospital, Binzhou, China. pioneersemailbox@sina.com

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• Oncology

OBJECTIVE: To investigate the biological function of microRNA-1179 (miRNA-1179) in regulating the proliferative and migratory abilities of the hepatocellular carcinoma (HCC) by targeting zinc-finger E-box-binding homeobox 2 (ZEB2).

PATIENTS AND METHODS: The miRNA-1179 level in 40 HCC tissues and matched normal tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association between the miRNA-1179 level and the clinical parameters of HCC patients was analyzed. The regulatory effects of miRNA-1179 on influencing proliferative and migratory abilities of HepG2 and Bel-7402 cells were assessed. The dual-luciferase reporter gene assay was conducted to verify the binding relationship between miRNA-1179 and ZEB2. Subsequently, the expression pattern and the biological function of ZEB2 in HCC were explored. The rescue experiments were finally carried out to uncover the role of the miRNA-1179/ZEB2 axis in regulating the progression of HCC.

RESULTS: MiRNA-1179 was downregulated in HCC tissues and cell lines. HCC patients with low expression of miRNA-1179 had higher metastatic rates (lymphatic metastasis and distant metastasis) and worse prognosis relative to those with low expression. The overexpression of miRNA-1179 attenuated the proliferative and migratory abilities of HCC cells. ZEB2 was confirmed to be the direct target of miRNA-1179 and its level was negatively regulated by miRNA-1179. ZEB2 was upregulated in HCC tissues and cell lines. The high expression of ZEB2 predicted a worse prognosis of HCC. The overexpression of ZEB2 reversed the inhibitory effects of miRNA-1179 on the proliferative and migratory abilities in HCC cells.

CONCLUSIONS: MiRNA-1179 is closely related to lymphatic metastasis, distant metastasis, and overall survival of HCC. It alleviates the malignant progression of HCC by downregulating ZEB2.

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