Inhibition of GARS1-DT Protects Against Hypoxic Injury in H9C2 Cardiomyocytes via Sponging miR-212-5p

J Cardiovasc Pharmacol. 2021 Nov 1;78(5):e714-e721. doi: 10.1097/FJC.0000000000001129.


The present study aimed to elucidate the function of long noncoding RNA GARS1-DT in hypoxia-induced injury in ex-vivo cardiomyocytes and explore its underlying mechanism. Hypoxic injury was confirmed in H9C2 cells by the determination of cell viability, migration, invasion, and apoptosis. GARS1-DT expression was estimated in H9C2 cells after hypoxia. We then measured the effects of GARS1-DT knockdown on hypoxia-induced H9C2 cells. The interaction between GARS1-DT and miR-212-5p was also investigated. Hypoxia treatment led to cell damage in H9C2 cardiomyocytes, accompanied with the upregulation of GARS1-DT expression. Transfection of GARS1-DT small interfering RNA remarkably attenuated hypoxia-induced injury by enhancing cell viability, migration, and invasion, and reducing apoptosis. Furthermore, GARS1-DT served as an endogenous sponge for miR-212-5p, and its expression was negatively regulated by GARS1-DT. The effects of GARS1-DT knockdown on hypoxia-induced injury were significantly abrogated by miR-212-5p silence. Besides, suppression of GARS1-DT activated PI3K/AKT pathway in hypoxia-treated H9C2 cells, which were reversed by inhibition of miR-212-5p. Our findings demonstrated the novel molecular mechanism of GARS1-DT/miR-212-5p/PI3K/AKT axis on the regulation of hypoxia-induced myocardial injury in H9C2 cells, which may provide potential therapeutic targets for acute myocardial infarction treatment.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Hypoxia
  • Cell Line
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Signal Transduction


  • MIRN212 microRNA, rat
  • MicroRNAs
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt