Upregulated lncRNA Pvt1 may be important for cardiac remodeling at the infarct border zone

Mol Med Rep. 2020 Oct;22(4):2605-2616. doi: 10.3892/mmr.2020.11371. Epub 2020 Jul 28.

Abstract

Myocardial infarction (MI) is a leading cause of mortality due to progression to ventricular arrhythmias (VAs) or heart failure (HF). Cardiac remodeling at the infarct border zone (IBZ) is the primary contributor for VAs or HF. Therefore, genes involved in IBZ remodeling may be potential targets for the treatment of MI, but the mechanism remains unclear. The present study aimed to explain the molecular mechanisms of IBZ remodeling based on the roles of long non‑coding RNAs (lncRNAs). After downloading miRNA (GSE76592) and mRNA/lncRNA (GSE52313) datasets from the Gene Expression Omnibus database, 23 differentially expressed miRNAs (DEMs), 2,563 genes (DEGs) and 168 lncRNAs (DELs) were identified between IBZ samples of MI mice and sham controls. A total of 483 DEGs were predicted to be regulated by 23 DEMs, among which Itgam, Met and TNF belonged to hub genes after five topological parameters were calculated for genes in the protein‑protein interaction network. These hub genes‑associated DEMs (mmu‑miR‑181a, mmu‑miR‑762) can also interact with six DELs (Gm15832, Gas5, Gm6634, Pvt1, Gm14636 and A330023F24Rik) to constitute the competing endogenous RNA (ceRNA) axes. Furthermore, a co‑expression network was constructed based on the co‑expression pairs between 44 DELs and 297 DEGs, in which Pvt1 and Bst1 were overlapped with the ceRNA network. Thus, Bst1‑associated ceRNA (Pvt1‑mmu‑miR‑181a‑Bst1) and co‑expression (Pvt‑Bst1) axes were also pivotal for MI. Accordingly, Pvt1 may be a crucial lncRNA for modification of cardiac remodeling in the IBZ after MI and may function by acting as a ceRNA for miR‑181a to regulate TNF/Met/Itgam/Bst1 or by co‑expressing with Bst1.

Keywords: myocardial infarction; infarct border zone; competing endogenous rna; long non-coding rnas; microrna; co-expression.

MeSH terms

  • Animals
  • Computational Biology
  • Databases, Genetic
  • Disease Models, Animal
  • Gene Regulatory Networks
  • Humans
  • Mice
  • MicroRNAs / genetics
  • Myocardial Infarction / complications
  • Myocardial Infarction / genetics*
  • RNA, Long Noncoding / genetics*
  • Up-Regulation*
  • Ventricular Remodeling / genetics*

Substances

  • MicroRNAs
  • PVT1 long-non-coding RNA, mouse
  • RNA, Long Noncoding