hsa_circ_0058092 protects against hyperglycemia‑induced endothelial progenitor cell damage via miR‑217/FOXO3

Int J Mol Med. 2020 Sep;46(3):1146-1154. doi: 10.3892/ijmm.2020.4664. Epub 2020 Jun 29.

Abstract

Circular RNAs (circRNAs) regulate the expression of genes that are critical for various biological and pathological processes. Previous studies have reported that the expression of hsa_circ_0058092 is decreased in patients with diabetes mellitus (DM); however, the specific role of this circRNA in DM is unknown. In the present study, endothelial progenitor cells (EPCs) were isolated and a decreased hsa_circ_0058092 expression was found under conditions of hyperglycemia (HG). The overexpression of hsa_circ_0058092 protected the EPCs against HG‑induced damage by preserving cell survival, proliferation, migration and angiogenic differentiation. The overexpression of hsa_circ_0058092 also decreased the HG‑induced increase in NADPH‑oxidase proteins and inflammatory cytokines. Further investigation revealed that the overexpression of hsa_circ_0058092 enhanced FOXO3 expression, which was mediated through the interaction with miR‑217. Furthermore, the upregulation of miR‑217 or the downregulation of FOXO3 abolished the protective effects of hsa_circ_0058092 against HG‑induced EPC damage. On the whole, these data suggest that hsa_circ_0058092 acts via the miR‑217/FOXO3 pathway to protect against EPCs HG‑induced damage, and to preserve the migration and angiogenesis of EPCs.

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / pathology*
  • Forkhead Box Protein O3 / genetics*
  • Humans
  • Hyperglycemia / genetics*
  • Hyperglycemia / pathology
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Up-Regulation

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN217 microRNA, human
  • MicroRNAs
  • RNA, Circular