RNA-binding protein CSTF2 promotes the proliferation and migration of hepatocellular carcinoma cells by regulating MCM6

Abstract

Abstract: Objective To explore the clinical significance of cleavage stimulation factor 2 (CSTF2) expresson in hepatocellular carcinoma (HCC), and its functional and molecular mechanism for the biology of HCC cells. Methods Public HCC-related datasets were collected and analyzed for the difference of CSTF2 expression between HCC and pericarcinoma tissues. Immunohistochemical analysis was used to validate the differential protein expression of CSTF2. The relationship between the expression level of CSTF2 and the clinical characteristics and prognosis of HCC patients was further analyzed. Correlation analysis was performed to identify those genes that are significantly related to CSTF2. In in vitro study, cultured HCC Cells were transfected with CSTF2 expression plasmid or MCM6 siRNA to up-regulate or down-regulate the genes' expression, respectively. CCK-8 test was used to analyze the proliferation. and wound healing assay was used to analyze the migration of HCC cells. The expression levels of CSTF2 and MCM6 in each group of cells were analyzed by qRT-PCR and western blot. Results CSTF2 was significantly up-regulated in cancer tissues in nine HCC microchips and two HCC RNA sequencing public data. High expression of CSTF2 indicated a lower overall survival rate and disease-free survival rate. The expression of CSTF2 was closely related to the tumor size, AFP level, TNM staging and vascular invasion of HCC patients. The expression of MCM6 mRNA in liver cancer tissue was positively correlated with that of CSTF2. Overexpression of CSTF2 promoted the proliferation and migration of HCC cells, and up-regulated the MCM6 level in the cells. Inhibiting the expression of MCM6 partially eliminated the cancer-promoting effect of CSTF2. Conclusion CSTF2 promotes HCC growth and metastasis via up-regulating MCM6. Both CSTF2 and MCM6 may become potential molecular targets for the treatment of HCC.

Key words: Hepatocellular carcinoma, RNA binding protein, CSTF2, MCM6, Proliferation, Migration

HE Xiao-yan, ZHANG Qiang-nu, YANG Liu, WANG Gui-zhi. RNA-binding protein CSTF2 promotes the proliferation and migration of hepatocellular carcinoma cells by regulating MCM6[J]. Chinese Hepatolgy, 2022, 27(2): 203-209.

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