Abstract

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

Highlights

  • Ischemic cardiomyopathy (ICM) is one of the most usual causes of death worldwide

  • Qiao et al reported that differentially expressed genes (DEGs) and transcription factors (TFs) play pivotal roles in ICM progress through regulating gene expression [12]

  • All DEGs between ICM and healthy controls were displayed in Supplementary Table S1

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Summary

Introduction

Ischemic cardiomyopathy (ICM) is one of the most usual causes of death worldwide. This study aimed to find the candidate gene for ICM. Ischemic cardiomyopathy (ICM), a common secondary cardiomyopathy, is one of the most common causes of death worldwide [1]. Many researchers have performed global gene expression to obtain key genes in the underlying mechanisms of ICM [9,10,11]. Qiao et al reported that differentially expressed genes (DEGs) and transcription factors (TFs) play pivotal roles in ICM progress through regulating gene expression [12]. Li et al found that the functional annotation and pathway analysis of DEGs was conducive to further studying the interactions between the differentially expressed genes in ICM [13]. The molecular mechanism of coordinating transcription in ICM has not been completely understood. It is essential to find the pathogenic mechanism and develop new diagnostic biomarker

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