The purpose of this paper is to study the effect of circRNA cerebellar degeneration–related protein 1 antisense RNA(CDR1as)/miR-671/GSK3β signaling pathway on PC12 cell injury and the mechanism of Exendin-4 (Ex-4) in PC12 cell injury protection. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circular RNA CDR1as and miR-671 in PC12 cells. By overexpressing or knocking out CDR1as, miR-671, and GSK3β, the role of CDR1as, miR-671, and GSK3β in PC12 cell injury was analyzed. The binding of CDR1as to miR-671 and GSK3β to miR-671 was verified by dual luciferase reporter assay. PC12 cells were treated with 1-methyl-4 phenyl-pyridine ion (MPP⁺) to construct a PC12 cell damage model. PC12 cell transfection experiments were used to confirm the role of CDR1as/miR-671/GSK3β signal axis in PC12 cell damage, and the role of Ex-4 in the association of circRNA CDR1as/miR-671/GSK3β signaling axis and PC12 cell damage. PC12 cell damage was detected by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cellular lactate dehydrogenase (LDH) release. Ex-4 reversed the phosphorylation levels of PI3K, AKT, and GSK-3β in MPP⁺-treated PC12 cells, and reduced MPP⁺-induced PC12 cell damage. CircRNA CDR1as upregulated the expression of GSK3β by sponge miR-671. Ex-4 downregulated CDR1as expression and upregulated miR-671 expression in MPP⁺-induced PC12 cell. Silencing of CDR1as reduced MPP⁺-induced PC12 cell damage. CDR1as transfection downregulated the expression of miR-671 in PC12 cells, promoted the expression and phosphorylated of GSK3β, and induced PC12 cell damage. GSK3β silencing reversed CDR1as-induced PC12 cell damage. CDR1as promoted the phosphorylation level of GSK3β in PC12 cells to cause cell damage; Ex-4 reversed the phosphorylation of GSK3β caused by CDR1as in PC12 cells and reduced the PC12 cell damage caused by CDR1as. Ex-4 reverses the damage of PC12 cells induced by CDR1as/miR-671/GSK3β signaling pathway.

本文旨在研究circRNA小脑变性相关蛋白1反义RNA(CDR1as)/miR-671/GSK3β信号通路对PC12细胞损伤的影响及Exendin-4(Ex-4)在PC12细胞中的作用机制。伤害保护。定量逆转录聚合酶链反应 (qRT-PCR) 用于检测 PC12 细胞中环状 RNA CDR1as 和 miR-671 的表达水平。通过过表达或敲除CDR1as、miR-671和GSK3β，分析了CDR1as、miR-671和GSK3β在PC12细胞损伤中的作用。CDR1as 与 miR-671 的结合以及 GSK3β 与 miR-671 的结合通过双荧光素酶报告基因测定来验证。PC12 细胞用 1-甲基-4 苯基-吡啶离子 (MPP ⁺) 构建 PC12 细胞损伤模型。PC12细胞转染实验证实CDR1as/miR-671/GSK3β信号轴在PC12细胞损伤中的作用，Ex-4在circRNA CDR1as/miR-671/GSK3β信号轴与PC12细胞损伤的关联中的作用. PC12 细胞损伤通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 和细胞乳酸脱氢酶 (LDH) 释放检测到。Ex-4 逆转了 MPP ⁺处理的 PC12 细胞中 PI3K、AKT 和 GSK-3β 的磷酸化水平，并减少了 MPP ⁺诱导的 PC12 细胞损伤。CircRNA CDR1as 通过海绵 miR-671 上调 GSK3β 的表达。Ex-4 在 MPP ⁺诱导的 PC12 细胞中下调 CDR1as 表达并上调 miR-671 表达。CDR1 沉默降低 MPP^{+ -}诱导 PC12 细胞损伤。CDR1as转染下调PC12细胞miR-671的表达，促进GSK3β的表达和磷酸化，诱导PC12细胞损伤。GSK3β 沉默逆转了 CDR1as 诱导的 PC12 细胞损伤。CDR1as促进PC12细胞中GSK3β的磷酸化水平引起细胞损伤；Ex-4 逆转了 PC12 细胞中由 CDR1as 引起的 GSK3β 磷酸化，并减少了由 CDR1as 引起的 PC12 细胞损伤。Ex-4 逆转 CDR1as/miR-671/GSK3β 信号通路诱导的 PC12 细胞损伤。