miR‑183‑5p attenuates cerebral ischemia injury by negatively regulating PTEN.

Cerebral ischemia is a common cerebrovascular disease caused by the occlusion of a cerebral blood vessel. MicroRNAs (miRNAs/miRs) are emerging regulators of various human diseases, including cerebral ischemia. Upregulation of miR-183-5p has been reported to alleviate liver injury induced by ischemia-reperfusion (I/R). However, the effect of miR-183-5p on cerebral ischemia injury remains unknown. The present study evaluated the effects of miR-183-5p on ischemia injury using ischemic models of mouse brains exposed to transient middle cerebral artery occlusion and Neuro-2A (N2A) neuroblastoma cells exposed to oxygen-glucose-deprivation (OGD) and subsequently reoxygenated. Ischemia was evaluated in mice using neurological function scores, cerebral edema, 2,3,5-triphenyltetrazoliumchloride, Nissl and Fluoro-Jade B staining assays. In addition, miR-183-5p expression, N2A cell viability and the expression levels of apoptosis-associated proteins were detected by quantitative PCR, Cell Counting Kit-8 assay, flow cytometry and western blotting. The association between miR-183-5p and phosphatase and tensin homolog (PTEN) was also confirmed by a luciferase reporter assay. The results revealed that miR-183-5p expression was decreased and brain damage was increased in ischemic mice compared with the sham group. Additionally, miR-183-5p levels were reduced, and apoptosis was increased in N2A cells exposed to ischemia compared with the control group. Following transfection with agomiR-183-5p, cerebral ischemic injury and apoptosis levels were reduced in thein vivoI/R stroke model and OGD-induced N2A cells. In addition, PTEN was determined to be a target of miR-183-5p following elucidation of a direct binding site. Overexpression of PTEN reversed the miR-183-5p-induced N2A cell apoptosis inhibition and survival after OGD. The results of the present study suggested that miR-183-5p reduced ischemic injury by negatively regulating PTEN, which may aid the development of a novel therapeutic strategy for cerebral ischemia.