Identification of F7 as a Hub Regulator in Hypertrophic Cardiomyopathy and Potential ceRNA Regulatory Network Based on Weighted Gene Co-expression Network Analysis

Abstract

Abstract Background. We identified a regulatory competing endogenous RNA (ceRNA) network and a hub gene for hypertrophic cardiomyopathy (HCM). Methods. We obtained microarray datasets of HCM tissue from NCBI Gene Expression Omnibus (GEO) and identified differentially expressed genes using the R package “limma.” Subsequently, differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs were matched using online databases. We identified relationships between key modules and HCM using weighted gene co-expression network analysis, whereas protein–protein interaction networks were constructed in STRING. To verify hub genes, we performed a gene set enrichment analysis. Real-time quantitative PCR and western blotting were performed to examine hub-gene expression in a mouse model of Ang-II infusion-induced cardiac hypertrophy. Results. We identified 271 upregulated and 368 downregulated lncRNAs in the GSE68316 dataset, along with 8 upregulated and 13 downregulated miRNAs in the GSE36946 dataset. We constructed a lncRNA–miRNA–mRNA ceRNA network in HCM using 6 downregulated lncRNAs, 1 upregulated miRNA, and 13 downregulated mRNAs. Another lncRNA–miRNA–mRNA ceRNA network in HCM was constructed with 15 upregulated lncRNAs, 1 downregulated miRNA, and 79 upregulated mRNAs. The results of WGCNA showed that black and turquoise modules were significantly related to HCM. Through Gene Ontology (GO) analysis, F7 was identified as a hub gene with network function enriched in neuroactive ligand–receptor interaction, cytokine–cytokine receptor interaction, and actin cytoskeleton regulation. Conclusions. This study reveals a potential molecular regulatory mechanism that could improve HCM diagnosis and treatment. Furthermore, the hub gene F7 might play an important role in HCM progression and be a valuable biomarker.