基于转录组学探讨心力衰竭和认知障碍的共同分子特征
Exploration of Common Molecular Features of Heart Failure and Cognitive Impairment Based on Transcriptomics
曾倩 1石瑀 2彭轲 2刘晓颖 2张奎 1柯雪雯 1谢颖豪 1奉水东 3韩桂圆 2李镒冲2
作者信息
- 1. 南华大学衡阳医学院公共卫生学院,湖南衡阳 421001;中国医学科学院阜外医院深圳医院国家心血管疾病临床医学研究中心·深圳,广东深圳 518057
- 2. 中国医学科学院阜外医院深圳医院国家心血管疾病临床医学研究中心·深圳,广东深圳 518057
- 3. 南华大学衡阳医学院公共卫生学院,湖南衡阳 421001
- 折叠
摘要
目的 利用生物信息学技术探究心力衰竭(heart failure,HF)和认知障碍共同的生物学过程及基因特征,为后续分子机制研究提供思路.方法 从基因表达综合数据库(gene expression omnibus,GEO)下载HF数据集GSE116250和认知障碍数据集GSE122063,鉴定出共同差异表达基因后,进行基因本体论(gene ontology,GO)富集分析,再应用String数据库和Cytoscape软件构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络筛选出中枢基因,在外部HF数据集GSE57338和认知障碍数据集GSE33000中验证中枢基因的表达,从JAS-PER和RegNetwork数据库中获得潜在的转录因子(transcription factor,TF)和微小RNA(micro RNA,miR)构建分子共调控网络.结果 共筛选出387个上调和388个下调差异基因(differential expressed genes,DEGs),主要富集在发育过程、细胞运动调节和主要组织相容性复合体(major histocompatibility complex,MHC)Ⅱ类蛋白复合物组装通路上.通过PPI网络鉴定出8个中枢基因(HLA-F、HLA-E、HLA-B、HLA-DRA、B2M、HLA-DQA1、HLA-DQB1、HSPA1A),主要通过内源性和外源性抗原加工和提呈通路激活免疫应答.在共调控网络中,FOXC1、GA-TA2、NFIC、NFYA、核转录因子-κB(nuclear factor-κB,NF-κB)1、miR-10是调控中枢基因的关键TFs和miR,潜在的NF-κB1/HLA-E/miR-10调控轴被认为在HF与认知障碍发展中发挥着重要作用.结论 本研究结果表明免疫调节可能在HF患者发生认知障碍的过程中发挥重要作用,可为研究"心-脑轴交互作用"提供新见解,但仍需进一步的分子生物学验证及人群研究证据.
Abstract
Objectives To explore the common biological processes and genetic characteristics between heart failure(HF)and cognitive impairment by bioinformatics technology,which provided basis for the subsequent molecular mecha-nisms research.Methods The HF dataset GSE116250 and cognitive impairment dataset GSE132903 were downloaded from the gene expression omnibus(GEO)database.After identifying the shared differential expressed genes,gene ontolo-gy(GO)enrichment analysis was performed.The protein-protein interaction(PPI)network was constructed by String da-tabase and Cytoscape software,and the hub genes were screened out.The expressions of hub genes were verified in exter-nal HF dataset GSE57338 and cognitive impairment dataset GSE33000.Potential transcription factors(TFs)and miro RNA(miR)were obtained from JASPER and RegNetwork repository used to construct a molecular co-regulatory net-work.Results A total of 387 up-regulated and 388 down-regulated differential expressed genes(DEGs)were screened out,which were mainly enriched in developmental process,cell motility regulation,and major histocompatibility com-plex(MHC)class Ⅱ protein complex assembly pathways.Eight hub genes(HLA-F,HLA-E,HLA-B,HLA-DRA,B2M,HLA-DQA1,HLA-DQB1,HSPA1A)were identified by PPI network,which activated immune responses mainly through endogenous and exogenous antigen processing and presentation pathways.In the co-regulatory network,FOXC1,GATA2,NFIC,NFYA,nuclear factor-κB(NF-κB)1 and miR-10 were the key TFs and miRs regulating the hub genes,and the potential NF-κB1/HLA-E/miR-10 regulatory axis was considered to play an important role in the devel-opment of HF and cognitive impairment.Conclusions The results of this study suggested that the immune regulation may play an important role in the development of cognitive impairment in patients with HF,which provided new insights into the"heart-brain axis interaction".However,further molecular biological verification and population study evidence are still needed.
关键词
心力衰竭/认知障碍/中枢基因/分子共调控网络/生物信息学分析Key words
heart failure/cognitive impairment/hub gene/molecular co-regulatory network/bioinformatics analysis引用本文复制引用
基金项目
广东省基础与应用基础研究基金(2023A1515010076)
广东省基础与应用基础研究基金(2021A1515220173)
深圳市医疗卫生三名工程项目(SZSM201811096)
中国医科院阜外医院深圳医院院内青年英才培育基金(YS-2022-006)
出版年
2024
NETL
NSTL
维普
万方数据