Abstract
Background
Accumulated evidence has established that long non-coding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to play a key role in tumorigenesis. However, the SNHG7 expression and its functional effects on PD remain uncharted.
Methods
RT-PCR was used to detect the expression of SNHG7, miR-425-5p and inflammatory cytokines in the plasma of PD patients and the healthy controls. Rotenone (Rot) was adopted to construct PD models in SD rats and SH-SY5Y cells, respectively. Gain- and loss- of functions of SNHG7 or miR-425-5p were conducted. The expression levels of Caspase3, tyrosine hydroxylase (TH), Iba1 in SD rat striatum was measured via immunohistochemistry and Western blot. Additionally, the expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α) and oxidative stress factors (MDA, SOD, GSH-PX) in the brain tissues were examined using RT-PCR and ELISA. Moreover, the protein levels of TRAF5, I-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 (RIP) assays were carried out to verify their interactions.
Results
SNHG7 was found up-regulated in PD patients while miR-425-5p expression was down-regulated (compared to healthy donors). Meanwhile, SNHG7 level was positively correlated with the level of inflammatory cytokines 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 microglia activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA (ceRNA) by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress.
Conclusion
Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress.
Increased level of NEAT1 long non-coding RNA is detectable in peripheral blood cells of patients with Parkinson’s disease