生物信息学分析TOP2A在肝细胞癌中表达和预后机制及其对肝癌增殖、迁移的影响

Bioinformatics Analysis of TOP2A Expression and Prognosis Mechanism in Hepatocellular Carcinoma and Its Effect on the Proliferation and Migration of Hepatocellular Carcinoma Cells

目的:探讨拓扑异构酶(DNA)Ⅱα[Topoisomerase(DNA)Ⅱalpha,TOP2A]在肝癌中的表达情况及敲低TOP2A对肝癌细胞HepG2增殖和迁移的影响。方法:通过TIMER 2.0在线数据库,分析TOP2A在肝癌组织和癌旁组织中的表达情况;利用HPA数据库得到TOP2A在不同肿瘤细胞系和TOP2A在不同肝癌细胞中的表达结果;使用GEPIA2数据库分析TOP2A在肝癌组织和癌旁组织中的表达差异以及与患者的生存预后的关系;Linkedomics在线数据库分析肝癌组织中TOP2A共表达的正负相关基因,对数据库筛选出的相关基因进行KEGG通路富集分析;细胞实验中降低TOP2A在肝癌细胞系中的表达,CCK-8和细胞划痕实验来检测TOP2A对肝癌细胞增殖和迁移的影响。结果:TOP2A在多种肿瘤组织中高表达且在肝癌细胞系中的表达明显上调;与低表达TOP2A患者相比,高表达TOP2A患者总生存周期较短;KEGG通路富集说明TOP2A可能参与细胞周期、DNA复制等多种过程;降低肝癌细胞HepG2中TOP2A表达后,细胞增殖和迁移能力明显降低。结论:TOP2A在肝癌患者中表达升高,降低TOP2A的表达可以抑制肝癌细胞系HepG2细胞增殖和迁移能力。

Objective:To investigate the expression of Topoisomerase(DNA)Ⅱalpha(TOP2A)in hepatocellular carcinoma and the effect of TOP2A knockdown on the proliferation and migration of HepG2 hepatocellular carcinoma cells.Methods:The expression of TOP2A in hepatocellular carcinoma and para-cancer tissues was analyzed by TIMER 2.0.The HPA database was used to obtain the expression of TOP2A in different tumor cell lines and hepatocellular carcinoma cells.The expression difference of TOP2A in hepatocellular carcinoma and adjacent tissues and the relationship with survival and prognosis of patients were analyzed using the GEPIA2 database.The positive and negative genes co-expressed in TOP2A in hepatocellular carcinoma were analyzed in the Linkedomics online database,and the related genes selected in the database were enriched by KEGG pathway.The expression of TOP2A in hepatocellular carcinoma lines was decreased in cell experiments,and the effects of TOP2A on the proliferation and migration of HCC cells were detected by CCK-8 and cell scratch experiments.Results:TOP2A is highly expressed in a variety of tumor tissues and significantly upregulated in hepatocellular carcinoma cell lines.Compared with patients with low expression of TOP2A,patients with high expression of TOP2A had shorter overall survival cycle.The enrichment of KEGG pathway suggests that TOP2A may be involved in various processes such as cell cycle and DNA replication.After reducing TOP2A expression in HepG2 cells,cell proliferation and migration ability were significantly reduced.Conclusion:The expression of TOP2A was increased in hepatocellular carcinoma patients,and decreasing the expression of TOP2A could inhibit the proliferation and migration of hepatoma cell line HepG2 cells.