Long non‑coding RNA XIST promotes cerebral ischemia/reperfusion injury by modulating miR‑27a‑3p/FOXO3 signaling

Zhang,Hua; Xia,Junyong; Hu,Qiushan; Xu,Liqin; Cao,Hongyan; Wang,Xu; Cao,Min

doi:10.3892/mmr.2021.12205

Long non‑coding RNA XIST promotes cerebral ischemia/reperfusion injury by modulating miR‑27a‑3p/FOXO3 signaling

Authors:
- Hua Zhang
- Junyong Xia
- Qiushan Hu
- Liqin Xu
- Hongyan Cao
- Xu Wang
- Min Cao
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Affiliations: Department of Neurosurgery, China Resources & WISCO General Hospital (CR & WISCO General Hospital Affiliated to Wuhan University of Science and Technology), Wuhan, Hubei 430080, P.R. China
Published online on: June 7, 2021 https://doi.org/10.3892/mmr.2021.12205
Article Number: 566
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cerebral ischemia/reperfusion (I/R) injury leads to neuronal damage, which may cause disability and even mortality. Multiple studies have revealed that long non‑coding RNAs (lncRNAs) serve pivotal roles in the pathogenesis of cerebral I/R injury. Therefore, the present study aimed to investigate whether the lncRNA X inactivate‑specific transcript (XIST) protects neuronal cells from cerebral I/R injury. In the present study, reverse transcription‑quantitative PCR demonstrated that XIST expression was upregulated in the brain tissues of an I/R mouse model and in oxygen and glucose deprivation/reperfusion (OGD/R)‑treated Neuro‑2a (N2a) cells. Knockdown of XIST alleviated cerebral injury, as well as reduced N2a cell apoptosis and reactive oxygen species (ROS) production. Additionally, luciferase reporter and RNA immunoprecipitation assays identified that XIST could bind with microRNA (miR)‑27a‑3p. It was found that miR‑27a‑3p expression was downregulated in the brain tissues of an I/R mouse model and in OGD/R‑induced N2a cells. In addition, miR‑27a‑3p overexpression attenuated I/R‑induced cerebral injury, and inhibited the apoptosis and ROS production of N2a cells. miR‑27a‑3p was found to target FOXO3. Silencing of FOXO3 alleviated cerebral injury, as well as inhibited N2a cell apoptosis and ROS production. Collectively, these findings indicated that XIST aggravated cerebral I/R injury by regulating miR‑27a‑3p/FOXO3 signaling, which may provide a novel insight into the treatment of cerebral I/R injury.

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