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 conductedto 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.
Highlights
As a typical neurodegenerative disorder disease, Parkinson's disease (PD) inflicts serious damage to the patients’ quality of life
Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, tyrosine hydroxylase (TH)-positive cell loss and microglia activation by mitigating inflammation and oxidative stress
The results indicated that compared with the healthy donors, SNHG7 was up-regulated in PD patients plasma, while miR-425-5p was downregulated (Fig. 1A, B)
Summary
As a typical neurodegenerative disorder disease, Parkinson's disease (PD) inflicts serious damage to the patients’ quality of life. As increasing research has focused on the pathogenic mechanism underlying PD, the causal genes of PD and non-coding RNAs (such as lncRNA and miRNA) that regulate these genes have attracted wider attention [4, 5]. An improved understanding of lncRNA in the PD pathogenesis/ carries great significance, promising to provide new insights for early diagnostic indicators and effective therapeutic targets of PD. 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. The SNHG7 expression and its functional effects on PD remain uncharted
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