Long non-coding RNA DANCR alleviates hypoxia-caused H9c2 cells damage through up regulation of HIF-1α

Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):533-541. doi: 10.1080/21691401.2020.1725026.

Abstract

Hypoxia is an important cause of myocardial cell loss, further inducing various heart illnesses, including acute myocardial infraction (AMI). Long non-coding RNA (LncRNA) discrimination antagonising non-protein coding RNA (DANCR) was firstly identified as epidermal cell differentiation suppressor. Here, we aimed to explore the effects and mechanism of DNACR in hypoxia-induced H9c2 cells. Hypoxic cells were made through 94% N2, 5% CO2, and 1% O2 environment for 24 h. Cell viability and apoptosis were detected via methyl thiazolyl tetrazolium (MTT) method and flow cytometry analysis, respectively. The expression of DANCR and HIF-1α was examined via qRT-PCR. The expression of proteins related to cell apoptosis and PI3K/AKT/mTOR and ERK1/2 signal pathways was examined through western blot analysis. We found that hypoxia induced obvious cell activity inhibition and apoptosis increasing in H9c2 cells. DANCR was negatively regulated under hypoxia condition. Overexpression of DANCR rescued activity and attenuated apoptosis. Moreover, the overexpression of DANCR elevated the activation of PI3K/AKT/mTOR and ERK1/2 pathways. Further study indicated that DANCR could up-regulate the expression of HIF-1α. Si-HIF-1α transfection could remove the beneficial effects of DANCR overexpression in hypoxia-caused H9c2 cells damage. In conclusion, DANCR alleviated hypoxia-caused H9c2 cells damage through positive regulation of HIF-1α.

Keywords: DANCR; HIF-1α; apoptosis; hypoxia; myocardial infarction.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Cell Survival
  • Gene Expression Regulation
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia / pathology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Rats
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Long Noncoding
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Mapk1 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3