RNA sequencing discloses the genome‑wide profile of long noncoding RNAs in dilated cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) is a common type of non-ischemic cardiomyopathy, of which the underlying mechanisms have not yet been fully elucidated. Long noncoding RNAs (lncRNAs) have been reported to serve crucial physiological roles in various cardiac diseases. However, the genome-wide expression profile of lncRNAs remains to be elucidated in DCM. In the present study, a case-control study was performed to identify expression deviations in circulating lncRNAs between patients with DCM and controls by RNA sequencing. Partial dysregulated lncRNAs were validated by reverse transcription-polymerase chain reaction. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and lncRNA-messenger RNA (mRNA) co-expression network analyses were employed to probe potential functions of these dysregulated lncRNAs in DCM. Comparison between 8 DCM and 8 control samples demonstrated that there were alterations in the expression levels of 988 lncRNAs and 1,418 mRNAs in total. The dysregulated lncRNAs were found to be mainly associated with system development, organ morphogenesis and metabolic regulation in terms of ‘biological processes’. Furthermore, the analysis revealed that the gap junction pathway, phagosome, and dilated and hypertrophic cardiomyopathy pathways may serve crucial roles in the development of DCM. The lncRNA-mRNA co-expression network also suggested that the target genes of the lncRNAs were different in patients with DCM as compared with those in the controls. In conclusion, the present study revealed the genome-wide profile of circulating lncRNAs in DCM by RNA sequencing, and explored the potential functions of these lncRNAs in DCM using bioinformatics analysis. These findings provide a theoretical foundation for future studies of lncRNAs in DCM.

[Retracted] Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy

“…As a recent study [ 23 ], Th1 and Th17 have been proposed as targets for the treatment of inflammatory DCM that is the main cause of heart failure among children as well as young adults [ 24 ]. Downregulated genes were significantly enriched in complement and coagulation cascades and phagosome, which were consistent with a previous study [ 25 ]. Based on the DEGs, we established a PPI network, composed of 171 up- and 136 downregulated genes.…”

“…Upregulated and hypomethylated genes and downregulated and hypermethylated genes were obtained by joint analysis of DEGs and DEMs. The biological functions of differentially BioMed Research International [11] GO:0046873 Metal ion ransmembrane transporter activity [27] GO:0005539 Glycosaminoglycan binding [17] GO:0022857 Transmembrane transporter activity [49] GO:0015318 Inorganic molecular entity transmembrane transporter activity [42] GO:0005249Voltage−gated potassium channel activity [11] GO:0015077 Monovalent inorganic cation transmembrane transporter activity [25] GO:0015079Potassium ion transmembrane transporter activity [15] GO type that exhibited the greatest influence on the same gene for the same specimen. The selected mutation data were saved into the Mutation Annotation Format (maf) format, which were visualized using the maftools package in R [15].…”

Identification and Functional Prediction of Long Non-Coding RNAs in Dilated Cardiomyopathy by Bioinformatics Analysis

“…Long non-coding RNAs (lncRNAs) are defined as transcripts >200 nucleotides in length and lacking known protein-coding function (Batista and Chang, 2013), although still capable of participating in many fundamental biological processes and pathophysiological events. Emerging evidence reveals critical roles for lncRNAs in the development and progression of cardiovascular diseases (Lovren et al, 2012;Han et al, 2014;Micheletti et al, 2017;Zhang et al, 2018), and several studies report dysregulation of lncRNAs in association with DCM (Frade et al, 2016;Li et al, 2018a;Huang et al, 2019;van Heesch et al, 2019;Zhang et al, 2019;Zhou et al, 2019). However, the mechanisms associated with lncRNA-specific regulation of DCM initiation and progression remain vague.…”

Long Non-coding RNA: A Key Regulator in the Pathogenesis of Diabetic Cardiomyopathy

“…Previous studies have reported that lncRNAs affect cardiac development, homeostasis, and regeneration. Abnormal expression of these lncRNAs is associated with the progression of cardiovascular diseases, and they may serve as diagnostic markers or therapeutic targets (32,33). However, the data regarding the action mechanism of lncRNAs in DCM are still limited, it is of great significance to study the potential function of lncRNAs in the development of DCM.…”