Long noncoding RNA SRY-box transcription factor 2 overlapping transcript participates in Parkinson’s disease by regulating the microRNA-942-5p/nuclear apoptosis-inducing factor 1 axis

ABSTRACT

Parkinson’s disease (PD) is a neurodegenerative disorder. Studies have shown that long noncoding RNA SRY-box transcription factor 2 overlapping transcript (lncRNA SOX2-OT) is highly expressed in PD patients, but its specific functions and mechanisms require further research. To address this gap, this study utilized an in vitro PD cell model induced by 1-methyl-4-phenylpyridinium (MPP⁺). Cell viability, apoptosis, lactate dehydrogenase (LDH) activity, inflammatory factor secretion, and oxidative stress indicators were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium bromide assay, LDH assay, flow cytometry, enzyme linked immunosorbent assay (ELISA), and corresponding kits, respectively. Gene and protein expression were measured using quantitative real-time-PCR and western blotting, respectively. The results indicated that microRNA-942-5p (miR-942-5p) was a direct target of lncRNA SOX2-OT and nuclear apoptosis-inducing factor 1 (NAIF1) was a direct target of miR-942-5p. The expression levels of lncRNA SOX2-OT and NAIF1 were increased, and miR-942-5p expression was decreased in SH-SY5Y cells following MPP⁺ treatment. In addition, MPP⁺ treatment reduced SH-SY5Y cell viability, increased apoptosis; increased cleaved caspase-3 protein expression and cleaved caspase-3/caspase-3 ratio; enhanced lactate dehydrogenase viability; increased tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and reactive oxygen species, and decreased superoxide dismutase activity in SH-SY5Y cells were inhibited by SOX2-OT-siRNA, and these inhibitions were reversed by miR-942-5p inhibitor. Moreover, the protective role of miR-942-5p mimic in MPP⁺-induced SH-SY5Y cells was eliminated by the NAIF1 plasmid. Overall, lncRNA SOX2-OT-mediated regulation of oxidative stress, inflammation, and neuronal apoptosis were directly controlled by the miR-942-5p/NAIF1 signal axis in MPP⁺-induced SH-SY5Y cells.

KEYWORDS:

• LncRNA SOX2-OT
• miRNA-942-5p
• NAIF1
• parkinson’s disease
• MPP⁺
• SH-SY5Y cells

Highlights

• MPP⁺ treatment increased lncRNA SOX2-OT and decreased miR-942-5p expression levels in SH-SY5Y cells.

• lncRNA SOX2-OT down-regulation relieved MPP⁺-induced SH-SY5Y cells injury via up-regulating miR-942-5p.

• miR-942-5p relieved MPP⁺-induced SH-SY5Y cells injury via down-regulating NAIF1 expression.

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.