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Circular RNA 0025984 Ameliorates Ischemic Stroke Injury and Protects Astrocytes Through miR-143-3p/TET1/ORP150 Pathway
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2021-08-25 , DOI: 10.1007/s12035-021-02486-8
Daixuan Zhou 1 , Zhi Huang 2 , Xiaoxi Zhu 3 , Tao Hong 4 , Yuanli Zhao 5
Affiliation  

MiR-143-3p is aberrantly expressed in patients with ischemic stroke and associated with ischemic brain injury. However, the underlying mechanisms are largely unknown. Here, we confirmed circ_0025984 and TET1 as a sponge and target of miR-143-3p, respectively, by luciferase reporter assay. In astrocytes, OGD significantly decreased circ_0025984 and TET1 levels but increased miR-143-3p levels, which was also observed in brains of mice with MCAO. Treatment with miR-143-3p inhibitor or circ_0025984 significantly decreased astrocyte apoptosis and autophagy, as well as cerebral injury and neuron loss in mice with MCAO. Notably, TET1 overexpression decreased astrocyte apoptosis and autophagy and induced promoter hypomethylation and expression of ORP150. Our results demonstrated for the first time that circ_0025984 protects astrocytes from ischemia-induced autophagy and apoptosis by targeting the miR-143-3p/TET1 pathway and might inhibit cerebral injury induced by ischemic stroke. Furthermore, our data revealed the important positive regulation of ORP150 by TET1, which could be associated with its neuroprotective role.



中文翻译:

Circular RNA 0025984 通过 miR-143-3p/TET1/ORP150 通路改善缺血性中风损伤并保护星形胶质细胞

MiR-143-3p 在缺血性中风患者中异常表达并与缺血性脑损伤有关。然而,潜在的机制在很大程度上是未知的。在这里,我们通过荧光素酶报告基因分析确认 circ_0025984 和 TET1 分别是 miR-143-3p 的海绵和靶标。在星形胶质细胞中,OGD 显着降低了 circ_0025984 和 TET1 水平,但增加了 miR-143-3p 水平,这也在 MCAO 小鼠的大脑中观察到。用 miR-143-3p 抑制剂或 circ_0025984 治疗显着降低了 MCAO 小鼠的星形胶质细胞凋亡和自噬,以及脑损伤和神经元丢失。值得注意的是,TET1 过表达降低了星形胶质细胞的凋亡和自噬,并诱导启动子低甲基化和 ORP150 的表达。我们的研究结果首次证明 circ_0025984 通过靶向 miR-143-3p/TET1 通路保护星形胶质细胞免受缺血诱导的自噬和凋亡,并可能抑制缺血性卒中诱导的脑损伤。此外,我们的数据揭示了 TET1 对 ORP150 的重要正向调节,这可能与其神经保护作用有关。

更新日期:2021-08-26
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