冠心病m6A修饰差异关键基因的筛选与验证  

Screening and verifying of key genes for m6A modification in coronary heart disease

作　　者：罗荔[1] 涅鲁排尔·热依木江 金颖 罗梅[1] LUO Li;Nerupal Reyimujiang;JIN Ying;LUO Mei(Department of Cardiology,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第五附属医院心血管内科,乌鲁木齐830011

出　　处：《新疆医科大学学报》2021年第6期683-690,共8页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金(2017D01C274)。

摘　　要：目的应用网络平台和生物信息学探讨冠心病m6A修饰差异基因,为临床研究和分子诊断提供理论支持。方法下载基因芯片数据集GSE113079和GSE64554,使用R语言limma对数据进行标准化,基于贝叶斯函数鉴定数据集的差异表达基因。筛选出所有m6A甲基化修饰基因,qPCR验证差异倍数排名前10的基因在冠心病患者PBMCs中的表达。R语言ClusterProfile对所筛选出的差异基因进行基因本体(GO)和基因组百科全书(KEGG)分析,String数据库分析差异基因编码蛋白的互作网络。受试者工作特征曲线(ROC)分析核心差异基因对冠状动脉疾病(CAD)预后的影响。结果从PBMCs、EAT、SAT中各筛选出598、298、316个差异基因。CAD患者中前10个差异基因中,HNRNPA2B1、IGF2BP2、ALKBH5和LRPPRC在冠心病患者PBMCs、EAT和SAT中表达量高,而WTAP、METTL14、FTO、HNRNPC、FMR1和YTHDF1在对照组中表达更高。qPCR方法验证FMR1的表达量与测序结果相反。GO富集分析可见这些差异基因主要与负调控翻译、mRNA稳态调控、RNA代谢等过程相关。KEGG分析这些基因富集在内质网蛋白过程、抗原处理和展示、心肌收缩等信号通路。蛋白互作分析表明HNRNPA2B1、YTHDF1、FTO等与其他基因存在较强的互作作用。ROC分析显示YTHDF1的诊断价值最佳。结论应用生物信息学可有效分析冠心病的m6A修饰差异基因,YTHDF1可作为预测冠心病的分子标记物。Objective With the help of network platform and bioinformatics to explore the differential gene of m6A modification of coronary heart disease,to provide theoretical support for clinical research and molecular diagnosis.Methods Gene chip data sets GSE113079 and GSE64554 were downloaded,R language limma were used to normalize the data,and differential expression of genes in the data set based on Bayesian function were identified.All m6A methylation modification genes were further screened out.The expression of the top 10 genes in the PBMCs of patients with coronary heart disease were verified by qPCR.The R language ClusterProfile package performed functional annotation(by GO)and pathway analysis(by KEGG)on the selected differential genes,and the String database analyzed the interaction network of the proteins encoded by the differential genes.ROC analyzed the influence of network core differential genes on the prognosis of CAD.Results A total of 598,298,and 316 differential genes were screened from PBMCs,EAT,and SAT,respectively.Among the top 10 differential genes in CAD patients,HNRNPA2B1,IGF2BP2,ALKBH5,and LRPPRC are highly expressed in PBMCs,EAT,and SAT in the patients with coronary heart disease,while WTAP,METTL14,FTO,HNRNPC,FMR1,and YTHDF1 are more highly expressed in the control group.The expression level of FMR1 is contrary to the sequencing results.GO enrichment analysis shows that these differential genes are mainly related to processes such as negative regulation of translation,regulation of mRNA stability,and RNA metabolism.KEGG analyzes the enrichment of these genes in signaling pathways such as endoplasmic reticulum protein processing,antigen processing and display,and myocardial contraction.Protein interaction analysis shows that HNRNPA2B1,YTHDC1,FTO,and etc.have strong interactions with other genes.ROC analysis shows that YTHDF1 has the best diagnostic value.Conclusion The application of bioinformatics can effectively analyze the m6A modified differential genes of coronary heart disease,YTHDC1 can be

关 键 词：冠心病 m6A 修饰 差异基因 生物信息学 

分 类 号：R714.21[医药卫生—妇产科学]