Identification of a lncRNA-miRNA-mRNA network based on competitive endogenous RNA theory reveals functional lncRNAs in hypertrophic cardiomyopathy.

Abstract

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease that affects 1 in every 200 people in the general population, leading to cardiac ischemia, heart failure and increased risk of sudden death. Recently, accumulating evidence has suggested that long noncoding RNAs (lncRNAs) may serve specific roles in various biological processes and participate in the pathology of various diseases, including HCM. Although a large number of lncRNAs have been detected, the functions of lncRNAs in HCM are still unknown. In the present study, a global triple network based on competitive endogenous RNA (ceRNA) theory was constructed using data from the National Center for Biotechnology Information Gene Expression Omnibus. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of mRNAs in the lncRNA-microRNA (miRNA)-mRNA network were performed using the Cytoscape plugins, BiNGO and Database. The lncRNA-miRNA-mRNA network was composed of 30 lncRNA nodes, 94 mRNA nodes and 8 miRNA nodes. Subsequently, hub nodes and the number of relationship pairs were analyzed and showed that 5 lncRNAs (ENST00000597346.1, ENST00000458178.1, ENST00000544461.1, ENST00000567093.1 and ENST00000571219.1) were closely related to HCM. Cluster module analysis and Random Walk with Restart of the ceRNA network further confirmed the potential role of two lncRNAs (ENST00000458178.1 and ENST00000567093.1) in HCM. The present study provides a new strategy for identifying potential pathways associated with HCM or other diseases. Furthermore, lncRNA-miRNA pairs may be regarded as candidate diagnostic biomarkers or potential therapeutic targets for HCM.