Downregulation of AC061961.2, LING01-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression

J Cell Physiol. 2019 Apr;234(4):4460-4471. doi: 10.1002/jcp.27247. Epub 2018 Sep 10.

Abstract

This study aimed to explore long noncoding RNAs (lncRNAs) implicated in dilated cardiomyopathy (DCM). Ten samples of failing hearts collected from the left ventricles of patients with DCM undergoing heart transplants, and ten control samples obtained from normal heart donors were included in this study. After sequencing, differentially expressed genes (DEGs) and lncRNAs between DCM and controls were screened, followed with functional enrichment analysis and weighted gene coexpression network analysis (WGCNA). Five key lncNRAs were validated through real-time polymerase chain reaction (PCR). Total 1,398 DEGs were identified, including 267 lncRNAs. WGCNA identified seven modules that were significantly correlated with DCM. The top 50 genes in the three modules (black, dark-green, and green-yellow) were significantly correlated with DCM disease state. Four core enrichment lncRNAs, such as AC061961.2, LING01-AS1, and RP11-557H15.4, in the green-yellow module were associated with neurotransmitter secretion. Five core enrichment lncRNAs, such as KB-1299A7.2 and RP11-13E1.5, in the black module were associated with the functions of blood circulation and heart contraction. AC061961.2, LING01-AS1, and RP11-13E1.5 were confirmed to be downregulated in DCM tissues by real-time PCR. The current study suggests that downregulation of AC061961.2, LING01-AS1, and RP11-13E1.5 may be associated with DCM progression, which may serve as key diagnostic biomarkers and therapeutic targets for DCM.

Keywords: differentially expressed gene (DEGs); dilated cardiomyopathy (DCM); long noncoding RNAs (lncRNAs); weighted gene coexpression network analysis (WGCNA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Circulation / genetics
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / physiopathology
  • Case-Control Studies
  • Disease Progression
  • Female
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Myocardial Contraction / genetics
  • Phenotype
  • Protein Interaction Maps
  • RNA, Long Noncoding / genetics*
  • Secretory Pathway / genetics
  • Signal Transduction / genetics*
  • Synaptic Transmission / genetics

Substances

  • RNA, Long Noncoding