SNHG14 Upregulation Was a Molecular Mechanism Underlying MPP+ Neurotoxicity in Dopaminergic SK-N-SH Cells via SNHG14-miR-519a-3p-ATG10 ceRNA Pathway.

Abstract

Long non-coding RNA small nuclear RNA host gene 14 (SNHG14) is a novel contributor of dopaminergic neuronal injury in Parkinson's disease. We further explored its role in 1-methyl-4-phenylpyridinium (MPP+)-damaged dopaminergic neurons (DAn) and the possible mechanism involving SNHG14, microRNA (miR)-519a-3p, and autophagy-related 10 (ATG10). MPP+ cytotoxicity was measured by MTS cell viability assay, flow cytometry, and a series of assay kits for detecting apoptosis and oxidative stress. Molecule expression was examined by qPCR and Western blotting, and RNA interaction was predicted by starBase2.0 of ENCORI platform and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. SNHG14 and ATG10 expression was increased, and miR-519a-3p was decreased in MPP+-treated SK-N-SH cells, and SNHG14 knockdown alleviated MPP+-induced SK-N-SH cell damage by regulating cell viability, cell cycle arrest, apoptosis, and oxidative stress. Additionally, antisense RNA of miR-519a-3p abated the suppressive role of SNHG14 knockdown, and ectopic expression of ATG10 counteracted the protective role of miR-519a-3p against MPP+ neurotoxicity. Mechanistically, SNHG14 and ATG10 were competitive endogenous RNAs (ceRNAs) for miR-519a-3p, and ATG10 expression could be positively modulated by SNHG14 via sponging miR-519a-3p. Target silencing SNHG14 and restoring miR-519a-3p could prevent DAn from MPP+ toxicity via regulation of ATG10.