miR-214-3p promotes the pathogenesis of Parkinson's disease by inhibiting autophagy

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. To date, there is still no effective treatment regimen for PD, which has prodromal stage, de novo stage (early stage) and advanced stage. Early diagnosis and intervention are paramount to prevent progression of this disease. We previously found that miR-214-3p was significantly up-regulated in the serums of prodromal and early PD patients. In this study, we confirmed that miR-214-3p was up-regulated in both MPP+-induced PD cell model and MPTP-induced PD mouse. Overexpression of miR-214-3p inhibited the cell activity and autophagy, and promoted apoptosis of dopaminergic neurons in vitro and in vivo, and aggravated the disease symptoms of animal model. Knockdown of miR-214-3p was able to restore the inhibition of autophagy and cell viability in both cell and animal model. Overexpression of autophagy-related gene 3 (ATG3) partially reversed the inhibition of autophagy and cell viability caused by overexpression of miR-214-3p in PD cell model. ATG3 is a member of the autophagy-related gene family and autophagy is involved in the pathological process of PD. BiBiServ2 website prediction showed that miR-214-3p could directly target ATG3. The western blot results showed that the protein expression of ATG3 could be down-regulated by miR-214-3p. Therefore, miR-214-3p may inhibit autophagy and activity of dopaminergic neurons and promote apoptosis by regulating the expression of ATG3. Our study provides a putative biomarkers and potential drug targets for early PD, which has important theoretical significance and clinical value.