Fudan University, Minhang Hospital, Shanghai, China.
Shanghai Medical College, Fudan University, Shanghai, China.
DNA Cell Biol. 2021 Jul;40(7):979-987. doi: 10.1089/dna.2020.6354. Epub 2021 Jul 6.
Long noncoding RNA X-inactive specific transcript (XIST) has been identified as a crucial regulator in neurodegenerative disorders. However, the role and mechanism of XIST in ischemic stroke remain elusive. In our study, we found that XIST expression was upregulated in both mice subjected to middle cerebral artery occlusion and oxygen-glucose deprivation (OGD)-treated neurons. Functional assays disclosed that the interference of XIST accelerated viability, and suppressed apoptosis and caspase-3 activity in OGD-treated neurons. Moreover, XIST interacted with miR-98, and miR-98 targeted BTB-to-CNC homology 1 (BACH1). miR-98 silencing or BACH1 overexpression counteracted XIST knockdown-mediated effects on cell viability and apoptosis in OGD-treated neurons. In conclusion, our data demonstrated that XIST facilitated the progression of ischemic stroke through regulating the miR-98/BACH1 axis. These findings might provide a novel therapeutic strategy for ischemic stroke treatment.
长链非编码 RNA X 失活特异性转录本（XIST）已被鉴定为神经退行性疾病的关键调节因子。然而，XIST 在缺血性中风中的作用和机制仍不清楚。在我们的研究中，我们发现 XIST 在大脑中动脉闭塞的小鼠和氧葡萄糖剥夺（OGD）处理的神经元中均上调表达。功能测定表明，XIST 的干扰可促进 OGD 处理的神经元的活力，并抑制细胞凋亡和半胱天冬酶-3 活性。此外，XIST 与 miR-98 相互作用，miR-98 靶向 BTB-to-CNC 同源性 1（BACH1）。miR-98 沉默或 BACH1 过表达可拮抗 XIST 敲低介导的 OGD 处理的神经元中细胞活力和细胞凋亡的作用。总之，我们的数据表明，XIST 通过调节 miR-98/BACH1 轴促进了缺血性中风的进展。这些发现可能为缺血性中风的治疗提供新的治疗策略。
