Upregulated lncRNA small nucleolar RNA host gene 1 promotes 1-methyl-4-phenylpyridinium ion-induced cytotoxicity and reactive oxygen species production through miR-15b-5p/GSK3β axis in human dopaminergic SH-SY5Y cells

Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been demonstrated to be upregulated and play a crucial role in the pathology of Parkinson's disease (PD). However, the exact role of SNHG1 and its underlying mechanisms in PD remains elusive. In this study, we found that SNHG1 and glycogen synthase kinase 3 beta (GSK3 beta) were upregulated, but miR-15b-5p was downregulated in 1-methyl-4-phenylpyridinium ion (MPP+)-treated SH-SY5Y cells. The upregulation of SNHG1 enhanced MPP+-induced cellular toxicity in SH-SY5Y cells, as shown by decreased cell viability, increased ROS production, and increased number of TdT-mediated dUTP Nick-End labeling-positive cells, accompanied with the upregulation of cleaved caspase 3 and elevation of cytochrome C release. Meanwhile, SNHG1 knockdown presented the converse effects. SNHG1 was demonstrated to interact with miR-15b-5p. Moreover, SNHG1 could attenuate the inhibitory effects of miR-15b-5p on MPP+-induced cytotoxicity and production of ROS. Besides, GSK3 beta was identified as a direct target of miR-15b-5p. The inhibitory effects of SNHG1 knockdown or miR-15b-5p overexpression on MPP+-induced cytotoxicity and reactive oxygen species (ROS) production were abrogated by upregulation of GSK3 beta. Taken together, these results demonstrate that upregulated lncRNA SNHG1 promotes MPP+-induced cytotoxicity and ROS production through the miR-15b-5p/GSK3 beta axis in human dopaminergic SH-SY5Y cells, suggesting that SNHG1 may act as a potential therapeutic target for PD treatment in the future.