ZNF7基因在乳腺癌中的表达及其共表达基因的生物信息学分析

Bioinformatics Analysis of ZNF7 Gene Expression and Its Co-expressed Genes in Breast Cancer

目的运用生物信息学方法研究锌指蛋白7(zinc finger protein 7,ZNF7)基因及其共表达基因在乳腺癌发生发展过程中的作用。方法通过GeneCards及PubMeb数据库分析ZNF7基因的已知功能;通过UALCAN网站分析ZNF7在乳腺癌患者中的表达情况,以及年龄、性别等因素对其表达的影响;通过Kaplan Meier-Plotter工具绘制ZNF7的生存曲线;利用LinkedOmics网站研究ZNF7的共表达基因,并对它们进行基因本体(gene ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析;通过STRING数据库分析ZNF7的蛋白-蛋白相互作用(protein-protein interaction,PPI)网络及其功能。结果ZNF7可能通过转录调控发挥炎症抑制和细胞保护活性,是特定肿瘤中强大的预后标志物,但其在乳腺癌中的角色尚不明确;ZNF7高表达患者生存率明显高于低表达患者,但其表达不受年龄、性别等因素的影响。GO富集结果显示,ZNF7正向共表达基因主要参与核糖核蛋白的生物合成、染色体分离、DNA复制等生物学过程,定位于细胞核,并与DNA及RNA的催化活性、解螺旋酶活性、单链DNA及mRNA结合等分子功能相关;KEGG通路富集表明,ZNF7主要涉及真核生物核糖体生物合成、剪接体、RNA转运、细胞周期、同源重组等通路。在PPI中,核因子κB激酶调节亚基γ抑制剂(inhibitor of nuclear factor kappa B kinase regulatory subunit gamma,IKBKG)和氧化应激诱导生长抑制剂家族成员2(oxidative stress induced growth inhibitor family member 2,OSGIN2)分别参与细胞凋亡和分裂;核糖体蛋白S7(ribosomal protein S7,RPS7)与核糖体蛋白L8(ribosomal protein L8,RPL8)参与核糖体生物合成;烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(nicotinamide adenine dinucleotide phosphate oxidase 4,NOX4)有助于超氧化物的产生。结论ZNF7可能通过参与乳腺癌患者体内多条信号通路的网络调控,从而影响乳腺癌的发生和发展。

Objective To investigate the role of zinc finger protein 7(ZNF7) and its co-expressed genes in the occurrence and development initiation and progression of breast cancer by bioinformatic approaches. Methods Known functions of ZNF7 gene was analyzed by GeneCards and PubMed databases;the expression of ZNF7 in breast cancer patients and the effects of age, gender and other factors on its expression were analyzed by UALCAN website;the survival curves of ZNF7 were plotted by Kaplan Meier-Plotter;the co-expressed genes of ZNF7 was studied by the LinkedOmics website, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed;the protein-protein interaction(PPI) network and its function of ZNF7 were analyzed by STRING database.Results ZNF7 might exert inflammatory inhibition and cytoprotection activities through transcriptional regulation, which was a powerful prognostic marker in specific tumors, however, its role in breast cancer remained unclear;survival rate of patients with high expression of ZNF7 was significantly higher than those with lower expression, while the expression of ZNF7 was not significantly influenced by age, gender or other factors. GO enrichment results showed that the positively co-expressed genes of ZNF7 were mainly involved in bioprocesses named ribonucleo protein complex biogenesis, chromosome segregation, DNA replication, etc, located in nucleus and related to molecular funtions named catalytic activity on DNA and RNA, helicase activity, single stranded DNA and mRNA binding, etc;KEGG pathway enrichment results revealed that ZNF7 were mainly involved in pathways named ribosome biogenesis in eukaryotes, sliceosome, RNA transport, cell cycle as well as homologous recombination, etc. In PPI, inhibitor of nuclear factor kappa B kinase regulatory subunit gamma(IKBKG) and oxidative stress induced growth inhibitor family member 2(OSGIN2) were respectively involved in cell apoptosis and devision;ribosomal protein S7(RPS7) and ribosomal protein L8(RPL8) were involved in ribonucleoprotein complex biogenesis;and nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4) could help the production of superoxides. Conclusion ZNF7 may join in the network regulation of multiple signaling pathways in breast cancer patients, thus affecting the initiation and progression of breast cancer.