RNA结合蛋白CSTF2通过调控MCM6促进HCC细胞的增殖和迁移  

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

作　　者：何晓燕[1] 张强弩 宰国真[1] 杨柳[1] 王桂芝 HE Xiao-yan;ZHANG Qiang-nu;YANG Liu;WANG Gui-zhi(Department of Pathology,The Fifth Affiliated Hospital of Zhengzhou University,Henan 450052,China;Department of Hepatopancreatobiliary Surgery,Shenzhen People's Hospital,Guangzhou 518020,China)

机构地区：[1]郑州大学第五附属医院病理科,河南450052 [2]深圳市人民医院肝胆胰外科

出　　处：《肝脏》2022年第2期203-209,共7页Chinese Hepatology

摘　　要：目的 探讨CSTF2在肝细胞癌(HCC)中的临床价值及其在HCC细胞中的功能和分子机制。方法 收集HCC公共数据,分析CSTF2的mRNA表达在癌组织和癌周组织中的差异。免疫组化分析CSTF2的蛋白表达在癌组织和癌周组织中的差异。分析CSTF2的表达水平与患者临床特征及预后的关系。相关性分析寻找与CSTF2存在显著相关性的基因。体外培养HCC细胞并采用体外转染过表达或siRNA的方式分别上调或下调细胞中的CSTF2及MCM6。CCK-8试验分析各组细胞的增殖情况,划痕实验分析各组细胞的转移情况。qRT-PCR和Western blot技术分析各组细胞的CSTF2及MCM6表达水平。结果 CSTF2在9个HCC的微芯片及2个HCC的RNA测序公共数据中,CSTF2均在癌组织中呈现显著上调。CSTF2的高表达预示着较低的总体生存率和无病生存率。CSTF2表达与HCC患者的肿瘤尺寸、AFP水平、TNM分期及血管侵袭等密切相关。肝癌组织中MCM6的mRNA表达与CSTF2水平呈正相关。过表达CSTF2可以促进HCC细胞的增殖和转移,同时过表达CSTF2可以上调MCM6的水平。抑制MCM6的水平可以部分消除CSTF2的促癌作用。结论 CSTF2可能通过调控MCM6在HCC中发挥促癌作用。CSTF2和MCM6可能成为HCC的潜在分子靶点。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 downregulate 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 MCM6level 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.

关 键 词：肝细胞癌 RNA结合蛋白 CSTF2 MCM6 增殖 转移 

分 类 号：R735.7[医药卫生—肿瘤]