Effects of miR-199a on autophagy by targeting glycogen synthase kinase 3β to activate PTEN/AKT/mTOR signaling in an MPP + in vitro model of Parkinson’s disease

作者：Rui-Qiong Ba, Jia Liu, Xijun Fan, Guili Jin, Bao-Gang Huang, Mingwei Liu, Jun-Su Yang · 发表于：Neurological Research · 年份：2020 · DOI：10.1080/01616412.2020.1726584 · 被引用次数：20 · 研究领域：Autophagy in Disease and Therapy、Electrospun Nanofibers in Biomedical Applications

Objectives: miR-199a can regulate autophagy, its underlying mechanisms remain unknown. The purpose of this study was to investigate the mechanisms of miR-199a involved in regulating autophagy in a 1-methyl-4-phenylpyridine (MPP+)-induced in vitro model of PD.Methods: PC12 cells were incubated in MPP+, and the expression levels of miR-199a were bidirectionally regulated via either transfection of an miR-199a mimic or incubation in miR-199a inhibitors. The experimental manipulations were divided into four groups, including the control group, MPP+ group, MPP+ + miR-199a mimic group, and MPP+ + miR-199a inhibitor group. MTT, CCK-8, qRT-PCR, Western blotting and linear correlation analysis were performed to evaluate various experimental indicators.Results: At increasing MPP+ concentrations, the following results were found: the expression levels of miR-199a, phosphorylated AKT and mTOR proteins expression decreased; the expression levels of phosphatase and tensin homologue (PTEN), GSK3β, Beclin1, and LC3II increased; PC12 autophagy increased; and cellular viability and survival rates decreased. Transfection of an miR-199a mimic increased miR-199a expression and induced all of the following: the expression levels of PTEN, GSK3β, Beclin1, and LC3II decreased; the expression levels of phosphorylated AKT and mTOR proteins expression increased; PC12 autophagy decreased; and cellular viability and survival rates increased.Discussion: In this in vitro study, we found that increasing miR-...