Downregulation of long noncoding RNA SNHG7 protects against inflammation and apoptosis in Parkinson's disease model by targeting the miR-425-5p/TRAF5/NF-κB axis.

Abstract

Accumulated evidence has manifested that long noncoding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to be involved in tumorigenesis. However, SNHG7 expression and its functional effects on PD remain uncharted. Rotenone (Rot) was adopted to construct PD models in Sprague-Dawley (SD) rats and SH-SY5Y cells, respectively. The expression levels of caspase 3, tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba1) in SD rat striatum were measured via immunohistochemistry and western blot. Additionally, the expressions of inflammatory cytokines (interleukin 1β [IL-1β], IL-6, tumor necrosis factor α) and oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase) in the brain tissues were examined using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Moreover, the protein levels of tumor necrosis factor receptor-associated factor (TRAF5), I-κB, nuclear factor-κB (NF-κB), HO-1, Nrf2 were detected via western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR-425-5p, and TRAF5. Dual-luciferase activity assay and RNA immunoprecipitation assays were conducted to verify their interactions. In comparison to healthy donors, SNHG7 was found upregulated while miR-425-5p expression was downregulated in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, TH-positive cell loss, and microglial activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress. Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress, and similar results were observed in the Rot-mediated rat model of PD.

• Authors: Haiquan Zhang, Zhiyong Wang, Keqi Hu, Handong Liu
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 35 Issue 10 Pg. e22867 (Oct 2021) ISSN: 1099-0461 [Electronic] United States
• PMID: 34369042 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• MIRN425 microRNA, human
• MicroRNAs
• NF-kappa B
• RNA, Long Noncoding
• TNF Receptor-Associated Factor 5
• TRAF5 protein, human

Topics

• Animals
• Apoptosis (genetics)
• Case-Control Studies
• Cell Line, Tumor
• Disease Models, Animal
• Down-Regulation (genetics)
• Humans
• Inflammation (genetics, metabolism)
• Male
• MicroRNAs (blood, genetics)
• NF-kappa B (metabolism)
• Neurons (metabolism)
• Oxidative Stress (genetics)
• Parkinson Disease (blood)
• RNA, Long Noncoding (blood, genetics)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (genetics)
• TNF Receptor-Associated Factor 5 (metabolism)
• Transfection