Circular RNA circSOX4 promotes the proliferation, migration and apoptosis of hepatocellular carcinoma cells by down regulating microRNA-432 expression

Z. Wen, Y.-X. Guo, H.-D. Sun

Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong, China. 45109882@qq.com

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• Oncology

OBJECTIVE: As the research of circular RNAs (circRNAs) in human malignant tumors has been increasing, multiple circRNAs have been discovered to be engaged in the modulation of the liver cancer cell functions. This study aims at exploring how circSOX4 affects the progression of hepatocellular carcinoma (HCC).

PATIENTS AND METHODS: CircSOX4 levels in HCC tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the relationship between circSOX4 expression and HCC patients’ prognosis was analyzed. CircSOX4 expression was knocked down by transfection of small interfering RNA. The effects of circSOX4 on cell functions including proliferation, invasiveness and migration ability were examined by cell counting kit-8 (CCK-8), transwell, cell wound healing test and flow cytometry experiments, respectively. The target RNA of circSOX4 was predicted through searching bioinformatics website, and the binding between the two was verified through Luciferase assay.

RESULTS: CircSOX4 was abnormally highly expressed either in HCC tissues or in cell lines, which was positively correlated with the poor prognosis of HCC patients. Transfection of small interfering RNA against circSOX4 in HCC cells resulted in inhibited migration and proliferation of HCC cells, while an increase in cell apoptosis. Bioinformatics analysis revealed that microRNA-432 contained the binding site pairing to circSOX4 3’UTR, and their binding relationship was confirmed by Luciferase assay. Their expression levels were negatively correlated. In addition, downregulation of microRNA-432 can partially reverse the effect of silenced circSOX4 on regulating apoptosis, proliferation and migration of HCC cells.

CONCLUSIONS: CircSOX4, highly expressed in HCC, indicates a poor prognosis. CircSOX4 may mediate the progression of HCC by binding to microRNA-432.

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