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

Zhu,Li; Zhou,Xueying; Li,Shanshan; Liu,Jianmeng; Yang,Jingyan; Fan,Xiangyun; Zhou,Shengnian

doi:10.3892/mmr.2020.11493

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

Authors:
- Li Zhu
- Xueying Zhou
- Shanshan Li
- Jianmeng Liu
- Jingyan Yang
- Xiangyun Fan
- Shengnian Zhou
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Affiliations: Department of Neurology, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Rehabilitation, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Neurology, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China, Department of Gynaecology and Obstetrics, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China, Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of General Medicine, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China
Published online on: September 7, 2020 https://doi.org/10.3892/mmr.2020.11493
Pages: 3944-3954
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 the in vivo I/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.

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