MicroRNA-203a-3p Regulates the Apoptosis of MPP+ Induced SH-SY5Y Cells by Targeting A-Synuclein

Abstract

Parkinson's disease (PD) is a universal central nervous system degenerative diseases and has a serious impact on people's lives. MicroRNA-203a-3p (miR-203a-3p) is a tumor-inhibiting factor. Nevertheless, the role and mechanism of miR-203a-3p in PD remain unclear. Therefore, this investigated the role and underlying mechanism of miR-203a-3p in PD. Firstly, we have established a PD cell model by treating SH-SY5Y cells with MMP+. We found that cell viability gradually decreased with increased MMP+ concentration. Subsequently, we choose 2000 μM MMP+ for subsequent experiments. Then, qRT-PCR assay demonstrated that miR-203a-3p was down-regulated in MMP+ treated SH-SY5Y cells. Next, results from TargetScan and dual luciferase reporter gene assay suggested that a-synuclein (SNCA), an important genetic risk factor of PD, had direct binding sites with miR-203a-3p. Subsequently, we confirmed that miR-203a-3p negatively regulated SNCA expression in SH-SY5Y cells. Finally, we investigated the influence of miR-203a-3p on MMP+ -induced SH-SY5Y cells. CCK-8 assay results showed that MMP + reduced cell proliferation and induced apoptosis were inhibited by miR-203a-3p up-regulation. In addition, we found that MMP+ enhanced expression of SNCA, p53 and cleaved Caspase-3 proteins was reduced by miR-203a-3p overexpression. However, these changes were reversed by SNCA-plasmid. In conclusion, miR-203a-3p regulated the apoptosis of MPP+ induced SH-SY5Y cells by targeting SNCA. miR-203a-3p/SNCA axis might be a new latent targets for PD therapy.