Construction of Molecular Network for Myocardial Ischemia-Reperfusion Injury Based on Ferroptosis-Related Genes and Its Validation Analysis
Objective To explore the expression and function of ferroptosis-related genes in myocardial ischemia-reperfusion(I/R)injury,and to provide new molecular targets for the treatment of myocardial I/R injury by constructing a molecular network and its verification analysis.Methods The gene expression data from the GSE108940 database were standardized,and differentially expressed genes(DEGs)were screened using volcano plots and heatmaps.Intersection analysis was performed with the FerrDb database to identify differentially expressed ferroptosis-related genes(DEFRGs).GO and KEGG functional enrichment analyses were conducted on these genes using the R package of cluster analyzer.The STRING database was employed to construct a protein-protein interaction(PPI)network,and key hub genes were evaluated using the Friends tool.The expression changes of these key genes were validated through the GSE4105 dataset and the hypoxia-reoxygenation(OGD/R)model of HL-1 mouse myocardial cell line.Results Based on the GSE108940 dataset,533 DEGs were identified through the standardized gene chip data,including 312 up-regulated genes and 221 down-regulated genes.Through further intersection analysis and comparison with ferroptosis-related genes in the FerrDb database,23 DEFRGs were identified,including 19 up-regulated and 4 down-regulated genes.The functional enrichment analysis of these genes covered multiple key biological processes,such as iron ion transport and intracellular iron ion homeostasis,and demonstrated their importance in various cellular components and molecular functional levels.The PPI network uncovered complex interactions among 20 gene nodes and identified five key hub genes:Sqstm1(Sequestosome 1),transferrin receptor(Tfrc),lipocalin 2(Lcn2),cyclin-dependent kinase inhibitor 1A(Cdkn1a),and solute carrier family 40 member 1(Slc40a1).Both the GSE4105 dataset and the constructed OGD/R model of HL-1 mouse myocardial cell line demonstrated significant expression changes of these key genes in the myocardial I/R injury model.Conclusion Based on bioinformatics methods,this study constructed a ferroptosis molecular network associated with myocardial I/R injury and initially validated the roles of key hub genes through experiments,providing potential targets for the treatment of myocardial I/R injury in the future.
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