Competitive binding of circCCDC6 to microRNA-128-3p activates TXNIP/NLRP3 pathway and promotes cerebral ischemia-reperfusion defects.

IF 1.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Acta biochimica Polonica Pub Date : 2023-11-07 DOI:10.18388/abp.2020_6552

ChongShu Wang, MingMing Dong, XiaoYi Zhang, XiaoYu Wang, Yan Zhao, Yunpeng Cao

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Abstract

Objective: Circular RNAs (circRNAs) are enriched in the brain and involved in various central nervous system diseases. The potential role of circCCDC6 in cerebral ischemia-reperfusion defects was partly elucidated in the work.

Methods: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and an oxygen-glucose deprivation and re-oxygenation (OGD/R)-treated SH-SY5Y cell model were constructed. CircCCDC6 expression in the two models was examined, and circCCDC6-involved mechanisms in neuronal pyroptosis and inflammation were analyzed through loss- and gain-of-function assays.

Results: MCAO/R rat brain tissues and OGD/R-treated SH-SY5Y cells exhibited upregulated circCCDC6. Silencing circCCDC6 attenuated neuronal pyroptosis and inflammation in the brain tissue of MCAO/R rats. Overexpressing circCCDC6 or inhibiting miR-128-3p stimulated OGD/R-induced pyroptosis and inflammation in SH-SY5Y cells, while upregulating miR-128-3p attenuated OGD/R injury. CircCCDC6 silencing-induced effects on SH-SY5Y cells were antagonized by TXNIP overexpression.

Conclusion: Mechanistically, circCCDC6 mediates miR-128-3p and activates TXNIP/NLRP3, thereby promoting OGD/R-induced neuronal pyroptosis and inflammation. CircCCDC6 may provide a new strategy for the treatment of MCAO/R.

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circCCDC6与microRNA-128-3p的竞争性结合激活TXNIP/NLRP3通路并促进脑缺血再灌注缺陷。

目的：环状核糖核酸（circRNAs）在大脑中富集，并与各种中枢神经系统疾病有关。circCCDC6在脑缺血再灌注缺陷中的潜在作用在该工作中得到了部分阐明。方法：建立大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型和糖氧剥夺再氧合（OGD/R）处理的SH-SY5Y细胞模型。检测了两种模型中CircCCDCC6的表达，并通过功能丧失和获得测定分析了CircCCDC6参与神经元焦下垂和炎症的机制。结果：MCAO/R大鼠脑组织和OGD/R处理的SH-SY5Y细胞的circCCDC6表达上调。CIRCDCD6的沉默减轻了MCAO/R大鼠脑组织中的神经元焦下垂和炎症。过度表达circCCDC6或抑制miR-128-3p刺激了OGD/R诱导的SH-SY5Y细胞的pyroptosis和炎症，而上调miR-128-3p减轻了OGD/R损伤。CircCCDCC6对SH-SY5Y细胞的沉默诱导作用被TXNIP过表达所拮抗。结论：从机制上讲，circCCDC6介导miR-128-3p并激活TXNIP/NLRP3，从而促进OGD/R诱导的神经元焦下垂和炎症。CircCCDC6可能为MCAO/R的治疗提供一种新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta biochimica Polonica 生物-生化与分子生物学

CiteScore

2.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Acta Biochimica Polonica is a journal covering enzymology and metabolism, membranes and bioenergetics, gene structure and expression, protein, nucleic acid and carbohydrate structure and metabolism.