Identification and Validation of Dilated Cardiomyopathy-Related Genes via Bioinformatics Analysis

Int J Gen Med. 2022 Apr 5:15:3663-3676. doi: 10.2147/IJGM.S350954. eCollection 2022.

Abstract

Purpose: Dilated cardiomyopathy (DCM) is a type of cardiomyopathy that can easily cause heart failure and has a high mortality rate. Therefore, there is an urgent need to study the underlying mechanism of action of dilated cardiomyopathy. In the present study, we aimed to explore potential miRNA-mRNA pairs and drugs related to DCM.

Methods: The Microarray data were collected from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis differentially expressed miRNAs and mRNAs in each microarray were obtained. The target genes of miRNAs were obtained from the miRWalk 2.0 database, and the intersection of these two gene sets (miRNA target genes and differentially expressed mRNAs in the microarray) was obtained. Pathway and Gene Ontology (GO) enrichment analyses were performed in the KOBAS database. Cytoscape software was used to construct the miRNA-mRNA network, and the final hub genes were obtained. Furthermore, we predicted several candidate drugs related to hub genes using DSigDB database. To confirm the abnormal expression of hub genes, qRT-PCR was performed.

Results: In total, eight differentially expressed miRNAs and 92 differentially expressed mRNAs were identified. In addition, 47 differentially expressed miRNA target genes were identified. According to the analysis results of the miRNA-mRNA network, we identified hsa-miR-551b-3p, hsa-miR-770-5p, hsa-miR-363-3p, PIK3R1, DDIT4, and CXCR4 as hub genes in DCM. Several candidate drugs, which are related to the hug genes, were identified.

Conclusion: In conclusion, in our study, we identified several hub genes that may be involved in the pathogenesis of DCM. Several drugs related to these hub genes may be used as clinical therapeutic candidates.

Keywords: dilated cardiomyopathy; drugs; mRNA; miRNA; public database.

Grants and funding

This study is supported by the National Natural Science Foundation of China (No. 82070303 and No. 82160073) and the Natural Science Foundation of Jiangxi, China (No.20192BAB215003).