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

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.

Acupuncture-Moxibustion Combined with Rehabilitation Training Is Conducive to Improving the Curative Effect, Cognitive Function, and Daily Activities of Patients with Cerebral Infarction

“…CI is a major threat to human health, which can lead to brain injury, disability, and even death worldwide [ 20 ]. The principle of TCM treatment of CI is to promote blood circulation and remove stasis, while acupuncture-moxibustion can not only improve blood circulation but also relieve muscle spasm of patients and enhance limb mobility [ 21 , 22 ].…”

Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia/reperfusion injury

“…Another recent study reported that expression of the lncRNA Neat1 was significantly decreased in OGD/R-induced BV-2 and N2a cells compared with that in control cells ( Zhou et al, 2022 ). The lncRNA XIST was also reported to be highly expressed in an MCAO/R-treated animal model and an OGD/R-treated cell model ( Zhang et al, 2021d ; Wang et al, 2021 ; Xiong et al, 2021 ). Wang et al also reported that the lncRNA XIST was upregulated in brain tissues under MCAO/R treatment and in OGD/R-treated PC12 cells ( Wang et al, 2021 ).…”

“…Furthermore, Xiong et al found that XIST was significantly highly expressed in SH-SY5Y cells after OGD/R treatment ( Xiong et al, 2021 ). Finally, another study identified that XIST expression was upregulated in the brain tissues of an I/R mouse model and OGD/R-induced N2a cells ( Zhang et al, 2021d ). The findings of these previous studies are in accordance with our results, indicating the robustness of our analysis.…”

“…In addition, Xiong et al reported that XIST reduced cell viability and induced cell apoptosis via modulating miR-486-5p and GAB2, which promoted cerebral I/R injury ( Xiong et al, 2021 ). Another two studies also indicated that knockdown of XIST inhibited brain injury by suppressing apoptosis and ROS production ( Zhang et al, 2021d ; Weng et al, 2021 ). Moreover, a recent study illustrated that Xist was involved in the regulation of pyroptosis in MCAO/R-treated rats and OGD/R-treated rat brain microvascular endothelial cells ( Guo et al, 2022 ).…”

Effect of remote limb ischemic post‐conditioning on the expression of miR‐21‐5p/PirB in the brain of rats with focal cerebral ischemia

“…Reperfusion of ischemic tissue through thrombolysis and interventional therapy can be used to treat ischemic stroke through embolized cerebral vascular recanalization, but this treatment method is associated with ischemia reperfusion injury (IRI) (Chen et al, 2016). IRI may result in neuronal damage that can lead to brain dysfunction and even death (Zhang et al, 2021). Moreover, not all patients with acute ischemic stroke could benefit from reperfusion therapies based on inclusion/exclusion criteria (Hern andez et al, 2021).…”