MicroRNA-361-3p Regulates Autophagy and Apoptotic Processes by Regulating PI3K/Akt Signaling in Parkinson’s Disease

Abstract

MicroRNAs are closely related to the pathogenesis of Parkinson’s disease (PD). The purpose of this study was to explore the effects of microRNA (miR)-361-3p on apoptosis and autophagy in 1-methyl-4-phenylpyridinium ion (MPP⁺) induced PD cell models, and its potential mechanisms. SH-SY5Y cells were induced by 1.0 mM MPP⁺ for 24 h to establish a PD cell model in vitro, and the expression level of miR-361-3p was regulated by cell transfection. Cell viability was detected by the Cell Count Kit (CCK)-8 method. Apoptosis was evaluated by flow cytometry. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The changes of autophagy-associated proteins (Beclin 1, LC3I, and LC3II) and PI3K/Akt signaling pathway-associated proteins (p-PI3K and p-Akt) were detected by Western blot. The target genes of miR-361-3p were predicted and functionally annotated by the bioinformatics method. The interaction between miR-361-3p and its target gene PFKFB3 was verified by the luciferase reporter gene. With the increase of MPP⁺ concentrations, the expression level of miR-361-3p and cell viability decreased gradually. In MPP⁺ induced SH-SY5Y cells, upregulation of miR-361-3p significantly improved cell survival and reduced apoptosis, while downregulating autophagy protein Beclin 1, LC3II/LC3I ratio, and increasing proteins p-PI3K/PI3K and p-Akt/Akt ratio. In addition, upregulation of miR-361-3p inhibited the expression of PFKFB3, while further overexpression of PFKFB3 negated the protective effect of miR-361-3p overexpression on MPP⁺ induced cells. This study showed that miR-361-3p was reduced in the PD cell model, and overexpression of miR-361-3p inhibited PD damage by regulating PFKFB3 and activating the PI3K/Akt signaling pathway.