Identification of Hub Genes Associated with Hypertension and Their Interaction with miRNA Based on Weighted Gene Coexpression Network Analysis (WGCNA) Analysis

Abstract

BACKGROUND Hypertension is one of the most widespread health conditions in the world, and the molecular mechanism of it is still unclear. In this study, we identified the hub genes (hub miRNA genes) associated with hypertension and explored the relationship between hypertension miRNA-gene by constructing a mRNA co-expression network and a miRNA co-expression network, which can help to reveal the mechanism and predict the prognosis of hypertension progression. MATERIAL AND METHODS Based on gene expression profile data of hypertensive samples from the Gene Expression Omnibus database, WGCNA was used to detect hypertension-related biomarkers and key mRNA and miRNA modules. Then, DAVID was used to perform gene-annotation enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) and miRPath were used for pathway analysis of mRNA and miRNAs genes. RESULTS We identified 3 key modules relating to hypertension, 2 mRNA modules named Msaddlebrown and Mgreenyellow and 1 miRNA module named Msalmon. In addition, 12 hub genes (RPL21, RPS28, LOC442727/PTGAP10, LOC100129599/RPS29P14, TBXAS1, FCER1G, CFP, FURIN, PECAM1, IGSF6, NCF1C, and LOC285296/UNC93B3) and 7 hub miRNAs (hsa-miR-1268a/b, hsa-miR-513c-3p, hsa-miR-4799-5p, hsa-miR-296-3p, hsa-miR-5195-5p, hsa-miR-219-2-3p, and hsa-miR-548d-5p) relating to hypertension were identified. HIF-1 signaling pathway and insulin signaling pathway were closely related to the 3 key modules. We also discovered 4 miRNAs (hsa-miR-548am-3p, hsa-miR-513c-3p, hsa-miR-182-5p, and hsa-miR-548d-5p) and 6 genes (IGF1R, GSK3B, FOXO1, PRKAR2B, HIF1A, and PIK3R1) were the core nodes in the hypertension-related miRNA-gene network, and hsa-miR-548am-3p was at the center of the network. CONCLUSIONS These findings will help improve the understanding of the pathogenesis of hypertension, and the discovered genes can serve as signatures for early diagnosis of hypertension.