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

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.

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Data availability

The datasets used and analyzed in the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The authors would like to express our gratitude for those who have critically reviewed this manuscript and those who give us help during this experiment.

Funding

The research was supported by Shenzhen “Sanming Project” (grant no.: SZSM201610039), Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District (Grand No. YL202001-14), and Scientific Research Project of Shenzhen Dapeng New District Medical and Health Group(Grand No. 2020JTLCYJ01).

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Yao Wang and Shangjie Chen were the guarantor of integrity of the entire study. Yulong Wang provided the study concepts. Yao Wang and Shangjie Chen designed the experiments. Weiyi Pan defined the intellectual content.

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Correspondence to Shangjie Chen.

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This study was approved by the Ethics Committee of Affiliated Baoan Hospital of Shenzhen, Southern Medical University.

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The author reports no conflicts of interest.

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Wang, Y., Pan, W., Wang, Y. et al. MicroRNA-32-5p attenuates cerebral ischemia/reperfusion injuries by modulating the phosphatase and tensin homologous protein. Metab Brain Dis 36, 2495–2504 (2021). https://doi.org/10.1007/s11011-021-00744-1

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Keywords

  • Cerebral ischemia/reperfusion injuries
  • MicroRNA-32-5p
  • PTEN
  • PI3K/AKT