Establishment and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA identifies functional genes in heart failure

Heart failure (HF), a common disease in adults, accounts for significantly global morbidity and mortality. Due to population aging, therapeutic progression in acute cardiovascular events, the prevalence of HF is increasing, in spite of the efficacy of multiple therapies for HF patients with decreased ejection fraction. Despite great progress in the underlying molecular mechanisms, it remains incompletely clear of the function of competing endogenous RNA (ceRNA) network in HF pathogenesis. Herein, we established an HF-related ceRNA network on the basis of differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) as well as mRNAs from GSE136547 and GSE124401 datasets. In brief, the ceRNA network composed of 58 mRNA nodes, 5 miRNA nodes, 82 lncRNA nodes as well as 252 edges. In addition, three lncRNAs (KCNQ1OT1, XIST and AC010336) with higher node degrees than other lncRNAs were chosen as hub nodes. At the same time, we have established five subnetwork of miR-17-5p, miR-20b-5p, miR107, miR-125a-5p and miR-140-5p centered ceRNA. Pathway analysis revealed the enrichment of ceRNA network in cell cycle pathways. Collectively, our research sheds new lights on the essential functions of ceRNA network in HF development, which also suggests possible application of these hub nodes as diagnostic biomarkers as well as therapeutic targets.

Automated summary

The study established an HF-related ceRNA network based on lncRNA, miRNA, and mRNA, revealing the importance of certain lncRNA as hub nodes. Five subnetworks were formed around miR-17-5p, miR-20b-5p, miR107, miR-125a-5p, and miR-140-5p, with enrichment in cell cycle pathways observed in the ceRNA network. The research sheds new light on the essential functions of the ceRNA network in HF development and suggests potential diagnostic and therapeutic applications of hub nodes.