ZNF521促进结肠癌的进展且受miR-211-5p靶向调控  

ZNF521 promotes the progression of colon cancer and is targetedly regulated by miRNA-211-5p

作　　者：杜静虎 陈满宇[1] 王东华[1] 陈钰[1] DU Jinghu;CHEN Manyu;WANG Donghua;CHEN Yu(Third Department of General Surgery,Xiangyang Central Hospital,Xiangyang Hubei 441021,China)

机构地区：[1]襄阳市中心医院普外三科,湖北襄阳441021

出　　处：《临床与病理杂志》2021年第6期1237-1247,共11页Journal of Clinical and Pathological Research

基　　金：襄阳市科技开发计划(2017-37)。

摘　　要：目的:探索锌指蛋白521(ZNF521)在结肠癌中的表达、功能和临床意义,并研究其机制。方法:采用免疫组织化学、蛋白质印迹法和q RT-PCR检测结肠癌组织或细胞系中ZNF521或mi R-211-5p的表达;采用小干扰RNA(small interfering,si RNA)和mi RNA模拟物分别构建ZNF521低表达和mi R-211-5p高表达细胞模型;采用CCK-8实验和Transwell实验分别检测细胞的增殖、迁移和侵袭;采用蛋白质印迹法检测凋亡相关蛋白Bax和Bcl-2的表达;通过Circ Interactome生物信息学网站预测、双荧光素报告基因实验验证mi R-211-5p与ZNF521的靶向关系。结果:与正常结肠组织相比,结肠癌患者标本中ZNF521表达显著增加,其高表达与患者TNM分期增加、分化程度低及局部淋巴结转移显著相关;体外实验证实,敲低ZNF521或过表达mi R-211-5p抑制了结肠癌细胞增殖、迁移和侵袭,并促进了结肠癌细胞凋亡;相关的机制研究证实,mi R-211-5p可以靶向ZNF521并负调节后者的表达。结论:ZNF521可作为致癌基因调节结肠癌细胞的增殖、迁移、侵袭和凋亡并受到mi R-211-5p的靶向调控。Objective:To explore the expression,function,and clinical significance of ZNF521 in colon cancer and its mechanism.Methods:Immunohistochemistry,Western blotting and q RT-PCR were used to detect the expression of ZNF521 and mi R-211-5p in colon cancer tissues or cell lines;small interfering RNA(si RNA)and mi RNA mimics were used to construct cell models with low expression of ZNF521 and high expression of mi R-211-5p respectively;CCK-8 and Transwell experiments were used to detect cell proliferation,migration and invasion,respectively.Western blotting was used to detect the expression of apoptosis-related proteins Bax and Bcl-2,and the targeting relationship between mi R-211-5p and ZNF521 was verified by the prediction of Circ Interactome bioinformatics website and the double fluorescein reporter gene experiment.Results:Compared with normal colon tissues,the expression of ZNF521 in colon cancer specimens significantly increased,and was correlated with TNM stage increase,the low degree of differentiation,and local lymph node metastasis.In vitro experiments showed that knocking down ZNF521 or overexpressing mi R-211-5p inhibited the proliferation,migration and invasion of colon cancer cells,and promoted apoptosis of colon cancer cells.Related mechanism studies confirmed that mi R-211-5p targeted ZNF521 and negatively regulate the expression of the latter.Conclusion:ZNF521 acts as a cancer-promoting molecule to regulate proliferation,migration,invasion and apoptosis of colon cancer cells and is targetedly regulated by mi R-211-5p.

关 键 词：ZNF521 结肠癌 增殖 迁移 侵袭 凋亡 miR-211-5p 

分 类 号：R735.35[医药卫生—肿瘤]