MiR-9-5p modulates the progression of Parkinson's disease by targeting SIRT1. (14th May 2019) - Wang, Zuobo
Highlights: miR-9-5p expression increased while SIRT1 decreased in MPP+-induced SH-SY5Y cells. miR-9-5p inhibition ameliorates MPP+-induced neurotoxicity in SH-SY5Y cells. SIRT1 is identified to be a target of miR-9-5p. miR-9-5p aggravates SIRT1-attenuated neurotoxicity in MPP+-treated SH-SY5Y cells. Abstract: Parkinson's disease (PD) is a most common progressive neurodegenerative disease mainly occurring in the elderly. Plenty of miRNAs are reported to involve in the progression of PD. However, the role of miR-9-5p in the regulation of PD pathogenesis remains unclear. The expressions of miR-9-5p and Sirtuin 1 (SIRT1) at mRNA and protein levels were determined by qRT-PCR and western blotting (WB) analyses. Cell viability and apoptosis were evaluated by MTT and flow cytometry. The levels of apoptosis-related proteins Bcl-2, Bax, Caspase-3 were detected by WB analysis. The releases of inflammatory cytokines IL-1β and TNF-α were examined by ELISA assay. ROS generation, LDH and SOD activity were evaluated using commercially available kits. Bioinformatics analysis, luciferase reporter, and qRT-PCR assays were performed to demonstrate the true interaction between miR-9-5p and SIRT1. Results showed miR-9-5p was upregulated and SIRT1 was downregulated in MPP + -treated SH-SY5Y cells in dose- and time- dependent manners. miR-9-5p knockdown attenuated MPP + -induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement in cell viability, and the suppression in cell apoptosis, inflammation, and oxidative stress. SIRT1 was identified to be a target of miR-9-5p. Restoration of miR-9-5p aggravated SIRT1-attenuated neurotoxicity in MPP + -treated SH-SY5Y cells. Our data suggested these data indicated that miR-9-5p exerted a neurotoxic role in MPP + -derived PD by directly targeting STAT1, providing a potential therapeutic strategy for patients troubled by PD.