Reconstruction and Analysis of the lncRNA-miRNA-mRNA Network Based on Competitive Endogenous RNA Reveal Functional lncRNAs in Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is an important cause of sudden death and heart failure with an unknown etiology. Recent studies have suggested that long non-coding RNA (lncRNA) can interact with microRNA (miRNA) and indirectly interact with mRNA through competitive endogenous RNA (ceRNA) activities. However, the mechanism of ceRNA in DCM remains unclear. In this study, a miRNA array was first performed using heart samples from DCM patients and healthy controls. For further validation, we conducted real-time quantitative reverse transcription (RT)-PCR using samples from DCM patients and a doxorubicin-induced rodent model of cardiomyopathy, revealing that miR-144-3p and miR-451a were down-regulated, and miR-21-5p was up-regulated. Based on the ceRNA theory, we constructed a global triple network using data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) and our miRNA array. The lncRNA-miRNA-mRNA network comprised 22 lncRNA nodes, 32 mRNA nodes, and 11 miRNA nodes. Hub nodes and the number of relationship pairs were then analyzed, and the results showed that two lncRNAs (NONHSAT001691 and NONHSAT006358) targeting miR-144/451 were highly related to DCM. Then, cluster module and random walk with restart for the ceRNA network were analyzed and identified four lncRNAs (NONHSAT026953/NONHSAT006250/NONHSAT133928/NONHSAT041662) targeting miR-21 that were significantly related to DCM. This study provides a new strategy for research on DCM or other diseases. Furthermore, lncRNA-miRNA pairs may be regarded as candidate diagnostic biomarkers or potential therapeutic targets of DCM.