Journal
METABOLIC BRAIN DISEASE
Volume 36, Issue 8, Pages 2495-2504Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-021-00744-1
Keywords
Cerebral ischemia/reperfusion injuries; MicroRNA-32-5p; PTEN; PI3K/AKT
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Funding
- Shenzhen Sanming Project [SZSM201610039]
- Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District [YL202001-14]
- Scientific Research Project of Shenzhen Dapeng New District Medical and Health Group [2020JTLCYJ01]
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This study demonstrated that miR-32-5p has neuroprotective effects against brain I/R injuries by modulating the PTEN/PI3K/AKT signaling pathway. Overexpression of miR-32-5p reduced brain damages in rats induced by MCAO/R, and PTEN was identified as a target of miR-32-5p. Additionally, miR-32-5p was able to activate PI3K/AKT signaling by inhibiting PTEN.
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. Graphic Abstract
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