MicroRNA-32-5p attenuates cerebral ischemia/reperfusion injuries by modulating the phosphatase and tensin homologous protein

Metab Brain Dis. 2021 Dec;36(8):2495-2504. doi: 10.1007/s11011-021-00744-1. Epub 2021 Oct 11.

Abstract

Non-coding RNAs have recently attracted much attention with the potential in the treatment of cerebral ischemia/reperfusion (I/R) injuries. In this study, we investigated the role of miR-32-5p in cerebral I/R injuries by using oxygen-glucose deprivation/reperfusion (OGD/R) PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R) rats. The expression of genes and proteins were detected by RT-qPCR and Western blot, respectively. The function of OGD/R PC12 cells was detected using MTT assay and flow cytometry analysis. The influences of MCAO/R on rats was evaluated by measuring the infarct volume and brain water content. Bioinformatics analysis and luciferase gene reporter assay were used to identify the relationship between miR-32-5p and PTEN. The results showed that miR-32-5p had neuroprotective effects on OGD/R induced PC12 cells and MCAO/R injured rats' brain. The level of miR-32-5p was significantly reduced after OGD/R. Overexpression of miR-32-5p significantly reduced MCAO/R-induced brain damages in rats. Moreover, PTEN was found to be a target of miR-32-5p, and overexpression of PTEN attenuated the effects of miR-32-5p overexpression on cerebral I/R injuries. In addition, miR-32-5p was able to activate PI3K/AKT signaling by inhibiting PTEN. In conclusion, miR-32-5p prevents brain I/R injuries through modulating PTEN/PI3K/AKT signaling pathway.

Keywords: Cerebral ischemia/reperfusion injuries; MicroRNA-32-5p; PI3K/AKT; PTEN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Infarction, Middle Cerebral Artery* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • PTEN Phosphohydrolase* / genetics
  • PTEN Phosphohydrolase* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Reperfusion Injury* / genetics

Substances

  • MIRN32 microRNA, rat
  • MicroRNAs
  • PTEN Phosphohydrolase
  • Pten protein, rat