Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

Int J Mol Med. 2020 Feb;45(2):451-460. doi: 10.3892/ijmm.2019.4441. Epub 2019 Dec 23.

Abstract

Circular RNAs (circRNAs) serve important roles in cardiovascular diseases, including myocardial infarction. However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) are not fully understood. In the present study, the roles of circRNA_101237 and let‑7a‑5p in cardiomyocyte death induced by A/R injury were investigated. It was identified that circRNA_101237 was induced by A/R injury in a time‑dependent manner and that circRNA_101237 knockdown protected cardiomyocytes from A/R‑mediated apoptosis. Additional mechanistic studies revealed that circRNA_101237 served as a sponge for let‑7a‑5p, subsequently regulating insulin‑like growth factor 2 mRNA‑binding protein 3 (IGF2BP3)‑dependent autophagy. IGF2BP3 downregulation decreased the levels of apoptosis and inhibited autophagy induced by A/R challenge in primary cardiomyocytes. These results identified circRNA_101237 as a novel circRNA that regulates cardiomyocyte death and autophagy, and demonstrated that the circRNA‑101237/let‑7a‑5p/IGF2BP3 axis, which serves as a regulator of cardiomyocyte death, may be a potential therapeutic target for the management of cardiovascular diseases.

MeSH terms

  • Animals
  • Apoptosis
  • Cells, Cultured
  • Down-Regulation
  • Gene Expression Regulation
  • Hypoxia / genetics*
  • Hypoxia / pathology
  • Mice
  • MicroRNAs / genetics*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology*
  • RNA, Circular / genetics*
  • RNA-Binding Proteins / genetics*

Substances

  • Igf2bp3 protein, mouse
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins
  • mirnlet7 microRNA, mouse