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LncRNA XIST Exacerbates Oxygen-Glucose Deprivation/Reoxygenation-Induced Cerebral Injury Through the miR-25-3p/TRAF3 Axis

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Abstract

Ischemic stroke causes lethal damage to the brain. Identifying key regulators of OGD/R-induced cerebral injury is important for developing novel therapies for ischemic stroke. HMC3 and SH-SY5Y cells were treated with OGD/R as an in vitro ischemic stroke model. Cell viability and apoptosis were determined via CCK-8 assay and flow cytometry. Inflammatory cytokines were examined by ELISA. Luciferase activity was measured for evaluating the interaction of XIST, miR-25-3p, and TRAF3. Bcl-2, Bax, Bad, cleaved-caspase 3, total caspase 3, and TRAF3 were detected via western blotting. HMC3 and SH-SY5Y cells showed increased XIST expression and decreased miR-25-3p expression following OGD/R. Importantly, silencing of XIST and overexpression of miR-25-3p reduced apoptosis and inflammatory response following OGD/R. Furthermore, XIST worked as a miR-25-3p sponge, and miR-25-3p targeted TRAF3 to suppress its expression. Moreover, the knockdown of TRAF3 ameliorated OGD/R-induced injury. Loss of XIST-mediated protective effects was reversed by overexpression of TRAF3. LncRNA XIST exacerbates OGD/R-induced cerebral damage via sponging miR-25-3p and enhancing TRAF3 expression.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the Hainan Provincial Cerebrovascular Disease Clinical Medical Center.

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  1. Department of Neurosurgery, Affiliated Haikou Hospital at Xiangya Medical College, Central South University, No. 43, People’s Avenue, Meilan District, Haikou, 570208, Hainan Province, People’s Republic of China

    You Li, Ji-Kun Zhang, Zheng-Tao Yu, Jun-Wen Jiang, Hong Tang, Guo-Long Tu & Ying Xia

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Contributions

Guarantor of integrity of the entire study: Ying Xia; study concepts: You Li; study design: You Li; definition of intellectual content: Ying Xia; literature research: You Li, Ji-Kun Zhang; experimental studies: You Li, Ji-Kun Zhang, Zheng-Tao Yu, Jun-Wen Jiang; data acquisition: Ji-Kun Zhang, Hong Tang; data analysis: You Li, Ji-Kun Zhang, Guo-Long Tu; statistical analysis: Ji-Kun Zhang, Jun-Wen Jiang; manuscript preparation: You Li; manuscript editing: You Li; manuscript review: Ying Xia; All the authors approved for the final version.

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Correspondence to Zheng-Tao Yu or Ying Xia.

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Li, Y., Zhang, JK., Yu, ZT. et al. LncRNA XIST Exacerbates Oxygen-Glucose Deprivation/Reoxygenation-Induced Cerebral Injury Through the miR-25-3p/TRAF3 Axis. Mol Neurobiol 60, 6109–6120 (2023). https://doi.org/10.1007/s12035-023-03450-4

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