Co‐expression Network Analysis of Altered lncRNAs and mRNAs in Diabetic Cardiomyopathy using Human iPSC‐derived Cardiomyocytes

Abstract

IntroductionMounting evidence in the past have substantiated the role of long‐non coding RNAs (lncRNAs) in diabetic cardiomyopathy (DCM). However, the pathogenesis of DCM remains unknown.AimThis study aimed to investigate the effect of the pro‐diabetic stimulus on the profile of lncRNAs and mRNAs, and the underlying co‐expression signaling network associated with DCM disease pathogenesis.ResultsOut of 40,173 lncRNAs and 20,730 mRNAs being screened, 1582 mRNAs and 2046 lncRNAs were differentially regulated (fold change>2.0, P<0.05) between DCM and control group of which more than half were intergenic and antisense lncRNAs. The subgroup analysis revealed more than 411 lncRNAs being co‐expressed with neighboring genes. To further investigate the potential regulatory role of these lncRNAs in gene regulation and the pathogenesis of DCM we constructed lncRNA‐mRNA co‐expression network which showed overall 48,155 significant co‐expression network connections. Moreover, in the DCM derived network, we had a comparatively greater number of nodes and connections than that in the control group. Majority of the dysregulated mRNAs of DCM co‐expression network were significantly enriched for the GO terms including actomyosin structure organization (GO:0031032), muscle contraction (GO:0006936), membrane raft assembly (GO:0001765), drinking behavior (GO:0042756), Focal adhesion (GO:0005925), skeletal muscle tissue development (GO:0007519), and cell‐matrix adhesion (GO:0007160) which have been associated with DCM in the past.ConclusionThis is the first study to investigate the genome‐wide lncRNA expression profile and co‐expression patterns with mRNA in DCM using microarray technology. These results provide comprehensive data about the pathways and regulatory mechanisms associated with DCM and indicate that lncRNAs may play a crucial role in DCM.Support or Funding InformationThis work was supported, in part, by a National Institutes of Health research grant P01GM 066730 (to Dr. Bosnjak) from the United States Public Health Services, Bethesda, Maryland, USA & DST‐UKEIRI DST/INT/UK/P‐50/2012 (to Dr. Anuradha Dhanasekaran) from the Department of Science and Technology, New Delhi, India.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.