LncRNA-XIST Competitively Binds to MicroRNA-532-5p to Regulate PTEN Expression, Exacerbating Cerebral Ischemia-Reperfusion Injury

Abstract

Cerebral ischemia-reperfusion injury (CIRI) is a severe neurological condition. LncRNA-XIST is closely associated with CIRI; however, its underlying mechanism remains unclear. A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in neuroblastoma cells (SH-SY5Y) were established. The expression of lncRNA-XIST, microRNA-532-5p, and PTEN was detected by qPCR. Binding sites between lncRNA-XIST and microRNA-532-5p, and between microRNA-532-5p and PTEN, were predicted using bioinformatic approaches and validated by dual-luciferase assays. Cell viability, apoptosis, and oxidative stress were assessed by CCK-8 assay, flow cytometry/Western blot, and MDA/SOD assay kits, respectively. LncRNA-XIST and PTEN were highly expressed in the MCAO/R rat brain tissues and the OGD/R cell model, whereas microRNA-532-5p was expressed at low levels. Knockdown of lncRNA-XIST attenuated OGD/R-induced cellular injury. Furthermore, lncRNA-XIST was found to target and inhibit microRNA-532-5p expression, while microRNA-532-5p in turn targeted and suppressed PTEN. The downregulation of PTEN expression and decrease in the apoptotic rate and oxidative stress levels induced by lncRNA-XIST knockdown in the OGD/R cell model were reversed by microRNA-532-5p knockdown. LncRNA-XIST promotes the development and progression of CIRI via the microRNA-532-5p/PTEN axis, offering potential therapeutic targets for CIRI.