阻塞性睡眠呼吸暂停综合征与心肌梗死后心力衰竭基因表达生物信息学分析

Bioinformatics analysis of gene expression in obstructive sleep apnea and heart failure following myocar-dial infarction

目的:采用生物信息学挖掘阻塞性睡眠呼吸暂停综合征(OSA)参与心肌梗死后心力衰竭(HF)的关键通路和核心分子。方法:从公共数据库GEO获得芯片数据,筛选与OSA、HF相关的差异表达基因,应用DAVID数据库和STRING数据库对于差异表达基因进行功能富集分析和构建蛋白质相互作用网络。使用Metascape平台获得交集基因和蛋白质模块分析结果作为候选核心分子,随后于PubMed文献数据库检索验证实验结果,确认关键通路及核心分子。通过miRTarbase数据库和Cytoscape软件运算分析取得关键通路的上游调控miRNA分子。结果:OSA相关的差异表达基因共265个,分子主要存在于细胞质和细胞核调节磷酸激酶活性。继发性HF相关基因共243个,大多数分子位于细胞膜上作为受体结合配体,参与信号转导等过程。结合候选分子和相关实验结果,确认NAMPT/SIRT3/SOD2为关键通路参与OSA-HF进程,而miR-183-3p、miR-4662a-5p、miR-6771-3p、miR-4803、miR-421是该通路上游调控miRNA分子。结论:生物信息学证据显示OSA与HF关系密切,NAMPT/SIRT3/SOD2通路及部分miRNA调控分子参与OSA-HF进程,为进一步研究提供新的思路。

Objective:To explore the key pathways and core molecules in the involvement of obstruc-tive sleep apnea syndrome(OSA)in heart failure(HF)following myocardial infarction from the genetic level.Methods:The differentially expressed genes(DEGs)related to OSA and HF were obtained from GEO data-base.Functional enrichment analysis and protein-protein interaction network of DEGs were analyzed by DAVID database and STRING database.The key gene candidates list is made of shared genes and predicted protein do-mains which are obtained via Metascape platform,and then experimental result were retrieved and verified in PubMed literature database to confirm key pathways and core molecules.The upstream regulatory miRNA mole-cules of key pathways were obtained through miRTarbase database and Cytoscape software.Results:There are 265 OSA-related differentially expressed gene mainly located in cytoplasm and nucleus to regulate phosphoki-nase activity.There are 243 secondary HF-related genes,most of which are located on plasma membrane as re-ceptor binding ligands and participate in signal transduction and other processes.Taking candidate molecules and verified experiments into consideration,NAMPT/SIRT3/SOD2 was confirmed as key pathway involved in OSA-HF process.Besides,miR-183-3p,miR-4662 A-5p,miR-6771-3p,miR-4803,and miR-421 might be the upstream regulatory miRNA molecules of the pathway.Conclusions:Bioinformatics evidence has showed that OSA is closely related to HF.NAMPT/SIRT3/SOD2 pathway and aboved miRNA may provide new basis and ideas for OSA-HF related studies.