LncRNA SNHG15 mediates 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal damage through targeting miR-29c-3p/SNCA axis

Abstract

ABSTRACT Background Parkinson’s disease (PD) is the most prevalent neurodegenerative disease in the elderly people. Long non-coding ribose nucleic acids (LncRNAs) can serve as molecular sponges for micro RNA (miRNA) and regulate gene expression, which is implicated in the occurrence and progression of PD. In this work, we investigated the functional role of lncRNA SNHG15 in a neuronal damage cell model and its potential mechanism. Methods SK-N-SH cells treated with 1-methyl-4-phenylpyridinium (MPP+) were employed as the in vitro cellular model to mimic neuronal degeneration. The expression levels of SNHG15, miR-29c-3p, and SNCA were determined by qRT-PCR. ELISA, CCK-8 proliferation assay, and flow cytometry were conducted to explore the effects of SNHG15 and miR-29c-3p on the production of inflammatory factors, cell proliferation, and apoptosis, respectively. Dual-luciferase reporter assay was utilized to validate the functional interactions among SNHG15, miR-29c-3p, and SNCA. SNCA protein levels were examined by Western blot. Results SNHG15 was highly induced in the cell model of MPP+-induced neuronal damage. SNHG15 knockdown significantly mitigated MPP+-induced damages in SK-N-SH cells. SNHG15 served as a sponge to down-regulate miR-29c-3p, thereby releasing the inhibition of miR-29c-3p on SNCA expression, which promoted neuronal damages upon MPP+ challenge. Conclusion The upregulation of SNHG15 upon MPP+ challenge mediates neuronal damages in SK-N-SH cells by regulating miR-29c-3p/SNCA axis. Future work is required to validate these findings in PD patients and animal models, which could provide insights into the diagnosis and therapy of PD.