LncRNA‐XIST Competitively Binds to MicroRNA‐532‐5p to Regulate PTEN Expression, Exacerbating Cerebral Ischemia‐Reperfusion Injury
Xudong Lu, Luhan Chen, Liqi Qian, Xiaoling Zhang, Yanping Wang, Bo YuABSTRACT
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.