Metab Brain Dis. 2020 Jun;35(5):753-763.doi:10.1007/s11011-020-00544-z. Epub 2020 Feb 21.

Neuroprotective effects of miR-532-5p against ischemic stroke

Jingwei Mu  1   2 Xi Cheng  1 Shanshan Zhong  1 Xiaohong Chen  2 Chuansheng Zhao  3 Affiliations

Abstract

Stroke can cause death and disability and has a high incidence with many complications. So far, effective treatment options for stroke are still limited. MicroRNA-532-5p (miR-532-5p) is significantly downregulated in stroke. However, the role of miR-532-5p in ischemic stroke is still unclear. In this study, we established an in vivo middle cerebral artery occlusion (MCAO) model in mice. The expression level of miR-532-5p, neurological score, infarct area, neuronal apoptosis, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway-related molecules were examined. Low miR-532-5p levels and high phosphatase and tensin homolog deleted on chromosome 10 (PTEN) levels were detected in the mouse MCAO model. MiR-532-5p overexpression improved neurological dysfunction, reduced the infarct area, attenuated neuronal injury and apoptosis, and promoted the activation of the PI3K/Akt signaling pathway in MCAO mice. In vitro, we treated mouse neuroblastoma cells (N2a) with oxygen-glucose deprivation and reperfusion (OGD/R). The expression level of miR-532-5p, cell viability, cell apoptosis, and the PI3K/Akt signaling pathway-related molecules were detected. Consistent with the in vivo tests, the miR-532-5p level was decreased and the PTEN level was increased in OGD-treated N2a cells in vitro. The miR-532-5p mimic increased cell viability, decreased cell apoptosis, and activated the PI3K/Akt signaling pathway. Furthermore, PTEN was verified as a target gene of miR-532-5p by luciferase reporter assay. PTEN overexpression attenuated the protective effect of miR-532-5p in OGD-treated N2a cells. In summary, these findings reveal that miR-532-5p protects against ischemic stroke by inhibiting PTEN and activating the PI3K/Akt signaling pathway and may serve as a novel therapeutic target for ischemic stroke.

Keywords: Ischemic stroke; PI3K/Akt signaling pathway; PTEN; miR-532-5p.

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