Abstract P2013: Genomic Identification Of Key CircRNAs In Healthy And Dilated Cardiomyopathy Human Heart

Abstract

Heart failure is a leading cause of morbidity and mortality. Dilated cardiomyopathy (DCM) is a primary cause of heart failure and sudden cardiac death worldwide. Therefore, it is important to identify factors that function in both normal and diseased hearts for a better understanding of etiology of DCM. CircRNA is a newly discovered class of RNA molecule and has been found to play a critical role in both physiological and pathological conditions. In this study, we systematically analyzed whole transcriptome data of five normal and five DCM human heart samples to identify putative key circRNAs and predict their potential underlying mechanisms. Our results revealed that many circRNAs produced from known cardiac diseases-related gene loci are dysregulated in DCM, such as circRNAs originated from TTN and RYR2 . Furthermore, our analysis revealed 40 conserved circRNAs that are putatively important in normal or DCM human heart, including 14 circRNAs with potential to act as sponges for DCM-related miRNAs and 4 circRNAs with potential coding ability. Importantly, our results identified that a novel class of circRNA, fusion-circRNAs are originated from MYH6 and MYH7 genes and exhibit most abundant expression in human heart with high conservation between different species. Furthermore, these fusion-circRNAs were dysregulated in DCM and have strong potential to sponge DCM-related miRNAs. In summary, our findings serve as a valuable resource for exploration of the function of circRNAs in human heart diseases.