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基于基因表达综合数据库鉴定缺血性心肌病的候选基因。

Identification of candidate genes in ischemic cardiomyopathy by gene expression omnibus database.

机构信息

Department of cardiac surgery, Capital medical university, Beijing Anzhen hospital, Beijing, China.

Department of cardiology, Capital medical university, Beijing Anzhen hospital, No.2, Anzhen Road, Chaoyan District, Beijing, 100029, China.

出版信息

BMC Cardiovasc Disord. 2020 Jul 6;20(1):320. doi: 10.1186/s12872-020-01596-w.

DOI:10.1186/s12872-020-01596-w
PMID:32631246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7336680/
Abstract

BACKGROUND

Ischemic cardiomyopathy (ICM) is one of the most usual causes of death worldwide. This study aimed to find the candidate gene for ICM.

METHODS

We studied differentially expressed genes (DEGs) in ICM compared to healthy control. According to these DEGs, we carried out the functional annotation, protein-protein interaction (PPI) network and transcriptional regulatory network constructions. The expression of selected candidate genes were confirmed using a published dataset and Quantitative real time polymerase chain reaction (qRT-PCR).

RESULTS

From three Gene Expression Omnibus (GEO) datasets, we acquired 1081 DEGs (578 up-regulated and 503 down-regulated genes) between ICM and healthy control. The functional annotation analysis revealed that cardiac muscle contraction, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy were significantly enriched pathways in ICM. SNRPB, BLM, RRS1, CDK2, BCL6, BCL2L1, FKBP5, IPO7, TUBB4B and ATP1A1 were considered the hub proteins. PALLD, THBS4, ATP1A1, NFASC, FKBP5, ECM2 and BCL2L1 were top six transcription factors (TFs) with the most downstream genes. The expression of 6 DEGs (MYH6, THBS4, BCL6, BLM, IPO7 and SERPINA3) were consistent with our integration analysis and GSE116250 validation results.

CONCLUSIONS

The candidate DEGs and TFs may be related to the ICM process. This study provided novel perspective for understanding mechanism and exploiting new therapeutic means for ICM.

摘要

背景

缺血性心肌病(ICM)是全球最常见的死亡原因之一。本研究旨在寻找 ICM 的候选基因。

方法

我们研究了 ICM 与健康对照之间差异表达的基因(DEGs)。根据这些 DEGs,我们进行了功能注释、蛋白质-蛋白质相互作用(PPI)网络和转录调控网络构建。使用已发表的数据集和定量实时聚合酶链反应(qRT-PCR)来验证所选候选基因的表达。

结果

从三个基因表达综合(GEO)数据集,我们获得了 1081 个 DEGs(578 个上调和 503 个下调基因),在 ICM 和健康对照组之间。功能注释分析表明,心肌收缩、肥厚型心肌病、致心律失常性右室心肌病和扩张型心肌病是 ICM 中显著富集的途径。SNRPB、BLM、RRS1、CDK2、BCL6、BCL2L1、FKBP5、IPO7、TUBB4B 和 ATP1A1 被认为是核心蛋白。PALLD、THBS4、ATP1A1、NFASC、FKBP5、ECM2 和 BCL2L1 是具有最多下游基因的前六个转录因子(TFs)。6 个 DEGs(MYH6、THBS4、BCL6、BLM、IPO7 和 SERPINA3)的表达与我们的整合分析和 GSE116250 验证结果一致。

结论

候选 DEGs 和 TFs 可能与 ICM 过程有关。本研究为理解 ICM 的机制和开发新的治疗方法提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d8c/7336680/b29631aea12d/12872_2020_1596_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d8c/7336680/b29631aea12d/12872_2020_1596_Fig7_HTML.jpg
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