MiRNA-103-3p targets Rab10 to activate the Wnt/β-Catenin signaling pathway to ameliorate corticosterone-induced injury in PC12 cells

Abstract

Abstract As a key regulatory molecule in neurological disorders, the mechanism by which Rab10 exerts its protective effect in neuronal cells in depression is currently unknown. This research aimed to explore the function and mechanism of action of Rab10, a gene associated with neuroprotection, by using an in vitro model of depression. PC12 cells induced by corticosterone (CORT) were used to simulate depression in vitro. The viability of PC12 cells was detected using a CCK-8 assay, and the interaction between miRNA-103-3p and Rab10 was confirmed by bioinformatics combined with double luciferase and RNA Binding Protein Immunoprecipitation (RIP) experiments. The level of miRNA-103-3p and Rab10 were detected using a quantitative PCR assay. The protein contents of Rab10, BDNF, CREB, P62, Beclin-1, Wnt3a, GSK3β, phosphorylated (p)-GSK3β, and β-catenin were detected by western blotting. The results indicated that the content of Rab10 was downregulated in CUMS rats and CORT-induced PC12 cells. Bioinformatics combined with double luciferase and RIP experiments showed that miRNA-103-3p targeted Rab10. Overexpression of Rab10 or silencing of miRNA-103-3p in CORT-induced PC12 cells activated the Wnt/β-catenin signaling pathway, upregulated the contents of BDNF, CREB, and Beclin-1, but downregulated the expression of P62 protein, whereas silencing Rab10 based on silencing miRNA-103-3p reversed the effect of miRNA-103-3p. Overall, our data indicated that miRNA-103-3p targeted Rab10 to activate the Wnt/β-catenin signaling pathway to increase cellular nerve plasticity and promote autophagy, thus resisting CORT-induced damage to PC12 cells.