Identification of Ferroptosis-related Genes and Their CeRNA Network in Hypertrophic Cardiomyopathy Based on Bioinformatic Analysis

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiomyopathy highly linked with the risk of sudden death and heart insufficiency in young people. The mechanics behind this condition are not comprehensively understood. However, emerging proof denotes the substantial involvement of ferroptosis in the onset and progression of cardiovascular illnesses. This study examines the connection between ferroptosis and hypertrophic cardiomyopathy, as well as the lncRNA-associated competing endogenous RNA (ceRNA) network of ferroptosis-related genes, using a bioinformatics approach. Methods： Four datasets (GSE180313, GSE36961, GSE188324, GSE197218) about HCM were retrieved from the GEO database. HCM-related module genes were identified by weighted gene co-expression network analysis (WGCNA) using the R WGCNA package. Ferroptosis-related genes were downloaded from the ferroptosis-related database FerrDb V2. Overlapping was performed to obtain the module genes associated with ferroptosis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R clusterprofiler package. The Protein–Protein Interaction (PPI) network was constructed using the STRING online analysis tool. The hub genes were identified using CytoHubba in Cytoscape. The expression of hub genes in cardiac tissues was examined using SPSS 27.0 statistic program. Then the lncRNA-associated ceRNA network was constructed using database prediction and Cytoscape software. Results: Sixty-four ferroptosis-related genes associated with HCM were identified through the use of WGCNA and FerrDB V2. Enrichment analysis showed that the pathways most highly enriched were related to lipid metabolism and iron ion homeostasis. From the PPI network construction and CytoHubba plug-in of Cytoscape, seven hub genes were obtained including PPARG, CD44, ACO1, SIRT1, CDKN2A, ADIPOQ, and TFRC. After validating in other gene expression datasets, we identified five hub-genes. These were then screened through ceRNA network construction, resulting in the identification of two key regulatory lncRNAs: NUTM2B-AS1 and XIST, along with two hub-genes, PPARG and CD. Conclusions: The hub genes (PPARG and CD44) may be regulated by the ceRNA regulatory network involving LncRNA XIST and NUTM2B-AS1, possibly influencing the pathogenesis of HCM in a ferroptosis regulatory manner.