Long noncoding RNA NEAT1 sponges miR‑125a‑5p to suppress cardiomyocyte apoptosis via BCL2L12

Mol Med Rep. 2019 May;19(5):4468-4474. doi: 10.3892/mmr.2019.10095. Epub 2019 Mar 27.

Abstract

Increasing evidence has suggested that long non‑coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has critical roles in multiple biological processes; however, few studies have reported on its function in heart disease. The present study indicated that NEAT1 expression is markedly downregulated in cardiomyocytes following ischemia/reperfusion injury in vivo and hydrogen peroxide treatment in vitro. Further experiments suggested that ectopic overexpression of NEAT1 suppresses cardiomyocyte apoptosis induced by hydrogen peroxide, as assessed by TUNEL assay and flow cytometry. In addition, using a dual‑luciferase reporter assay, NEAT1 was demonstrated to directly interact with microRNA (miR)‑125a‑5p and overexpression of miR‑125a‑5p efficiently reversed the stimulatory effect of NEAT1 on B‑cell lymphoma‑2‑like 12 (BCL2L12) expression. Furthermore, the results indicated that NEAT1 inhibits cardiomyocyte apoptosis via regulating the expression of BCL2L12, which appeared to be mediated via miR‑125a‑5p. In conclusion, the present study suggested that NEAT1 functions as a miR sponge to inhibit cardiomyocyte apoptosis and may be a novel therapeutic target for cardiomyocyte apoptosis‑associated heart diseases.

MeSH terms

  • Animals
  • Antagomirs / metabolism
  • Apoptosis* / drug effects
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Down-Regulation / drug effects
  • Hydrogen Peroxide / pharmacology
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Ago2 protein, mouse
  • Antagomirs
  • Argonaute Proteins
  • MicroRNAs
  • NEAT1 long non-coding RNA, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • Hydrogen Peroxide