Integrated bioinformatics analysis to identify potential key genes of ferroptosis mechanism in myocardial in-jury caused by SARS-CoV-2 infection
You Hongjun
Zhao Qianqian
Gou Qiling
Chang Fengjun
Diao Jiayu
Dong Mengya
Abstract：Objective Ferroptosis plays a causative role in COVID-19-related cardiovascular disorders.The current study aimed to identify the potential ferroptosis-related key genes in the pathogenesis of myocardial damage caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Methods Bioinformatics analyses of the transcriptional profiling of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)infected with SARS-CoV-2 were investigated,including ferroptosis-related differentially expressed genes(DEGs)identification,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses,protein-protein interactions(PPI),hub genes identification,and TF-gene interactions to explore the potential roles of ferroptosis-related genes in the pathogenesis of COVID-19-related myocardial damage.Furthermore,exploitation of candidate drugs targeting hub genes was also explored to provide theoretical basis for its treatment.Results Eighty genes were identified as ferroptosis-related DEGs by comparing transcriptional profiling of hiPSC-CMs infected with or without SARS-CoV-2 and subsequent intersecting with FerrDb.GO and KEGG pathway enrichment analyses indicated that these ferroptosis-related genes involved in the cellular response to oxidative stress and hypoxia,ferroptosis,necroptosis,HIF-1 signaling pathway,TNF signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,and et al.Identified hub genes using PPIs and cytoHubba were IL-6,JUN,PTGS2,TLR4,HIF1A,CAV1,HMOX1,SIRT1,EGFR,and ATF3.TFs,namely RELA,NFKB1,EGR1,STAT3,JUN and SP1 interacted with most hub genes.Candidate drugs targeting hub genes were identified,namely deferoxamine,oxygen,simvastatin,N-Acetyl-L-cysteine,curcumin,acetovanillone,resveratrol,glutathione and et al.Conclusions Our comprehensive bioinformatics analyses of transcriptional profiling of hiPSC-CMs infected with SARS-CoV-2 provided us with a novel view of ferroptosis-related pathogenesis of myocardial damage caused by SARS-CoV-2 infection.Furthermore,exploitation of candidate drugs targeting ferroptois-related genes holds great promise in the future fight against this form of myocardial damage.
Keywords：SARS-CoV-2COVID-19CardiomyocytesFerroptosis
Publication Date：2024-07-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 772-777 )