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. 2021 Apr;71(4):778-789.
doi: 10.1007/s12031-020-01698-2. Epub 2020 Sep 5.

Exendin-4 Reversed the PC12 Cell Damage Induced by circRNA CDR1as/miR-671/GSK3β Signaling Pathway

Hui Quan #  1 , Qiudan Chen #  2 , Kesheng Wang  3 , Qinwan Wang  3 , Meiling Lu  3 , Yue Zhang  3 , Sujing Qiang  3 , Shaobo Xue  3 , Lin Han  3 , Huanhuan Zhu  3 , Qiangyuan Fan  3 , Meiyu Bao  3 , Weixin Xu  4 , Weifeng Wang  5
Affiliations

Exendin-4 Reversed the PC12 Cell Damage Induced by circRNA CDR1as/miR-671/GSK3β Signaling Pathway

Hui Quan et al. J Mol Neurosci. 2021 Apr.

Abstract

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.

Keywords: Circular RNA; Exendin-4; GSK3β; circRNA cerebellar degeneration–related protein 1 antisense RNA; miR-671.

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