Abstract
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.
Highlights
Chronic heart failure (CHF), a main cause of morbidity and mortality, especially in aging
To further investigate the crosstalk between mRNAs and long non-coding RNA (lncRNA), we performed bidirectional hierarchical clustering by using R package “gplot.” In the heat map, we discovered two modules (Figures 5A–C) that were highly related to Dilated cardiomyopathy (DCM)
DCM is an important cause of sudden cardiac death (SCD) and heart failure and is the major indication of cardiac transplantation in children and adults worldwide
Summary
Chronic heart failure (CHF), a main cause of morbidity and mortality, especially in aging. The lifetime risk of developing CHF has been calculated to range from 20 to 33% worldwide, and nearly half of the patients with CHF will. CeRNA Network in Dilated Cardiomyopathy die within 5 years despite all the advanced therapies (Dobre et al, 2014). As the population ages, the cost associated with CHF is expected to increase substantially. The etiology of CHF can be classified as ischemic (ICM) or non-ischemic cardiomyopathy (NICM), and dilated cardiomyopathy (DCM) is one of the major causes of ICM. In contrast to revascularization therapies for ICM, novel treatments for DCM remain scarce. Studies focused on developing new strategies for DCM are urgently required
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