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

BackgroundAccumulated 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. MethodsRT-PCR was used to detect the expression of SNHG7, miR-425-5p and in ammatory 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 in ammatory 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. ResultsSNHG7 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 in ammatory cytokines in PD patients. Functional experiments con rmed 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 in ammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA (ceRNA) by sponging miR-425-5p and promoted TRAF5 mediated in ammation and oxidative stress. ConclusionInhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated in ammation and oxidative stress.

Competing endogenous RNA (ceRNA) networks in Parkinson's disease: A systematic review

“…SNHG7 is an oncogenic lncRNA on chromosome 9q34.2 and is highly expressed in cancer cells and tumors (Bian et al, 2020 ). Tumor necrosis factor receptor-associated factor 5 (TRAF5) is a cytoplasmic adapter that can trigger the NF-κB signaling pathway via its receptors and can take part in modulating nerve cell death, inflammatory reactions, and other neurological processes (Zhang et al, 2021 ). Zhang et al demonstrated that in PD, SNHG7 works as a ceRNA by sponging miR-425-5p and promoting TRAF5 (Zhang et al, 2021 ).…”

“…Tumor necrosis factor receptor-associated factor 5 (TRAF5) is a cytoplasmic adapter that can trigger the NF-κB signaling pathway via its receptors and can take part in modulating nerve cell death, inflammatory reactions, and other neurological processes (Zhang et al, 2021 ). Zhang et al demonstrated that in PD, SNHG7 works as a ceRNA by sponging miR-425-5p and promoting TRAF5 (Zhang et al, 2021 ). In addition, SNHG10 is a lncRNA located on chromosome 14q32.13 and is involved in advancing several types of cancer (Sun Z. M. et al, 2022 ).…”

The Role of Non-Coding RNAs in the Pathogenesis of Parkinson’s Disease: Recent Advancement

“…With HOTTIP sponging to miR-615-3p, HOTTIP downregulation alleviates microglial activation, pro-inflammatory cytokine secretion and neuron death by lowering the expression of FOXO1 [ 183 ]. By binding to the miR-425-5P/TRAF5 axis, SNHG7 serves as a ceRNA to modulate inflammation and oxidative stress in cell and mouse models [ 184 ].…”

Crosstalk between regulatory non-coding RNAs and oxidative stress in Parkinson’s disease

“…Among the 17 newly studied lncRNAs, 13 were identified to aggravate oxidative stress and inflammatory responses in neurons, namely AL049437, HOTAIR, LINC00943, lncRNA-p21 (lnc-p21), MIAT, NEAT1, rhabdomyosarcoma 2-associate transcript (RMST), SNHG1, SNHG7, SOS1 intronic transcript 1 (SOS1-IT1), SRY-box transcription factor 2 overlapping transcript (SOX2-OT), taurine upregulated gene 1 (TUG1), and UCA1 (Cai et al, 2019 ; Ding et al, 2019 ; Zhai et al, 2020 ; Zhang L. et al, 2020 ; Zhao et al, 2020b ; Guo et al, 2021 ; Lian et al, 2021 ; Ma et al, 2021a ; Zhang et al, 2021 ; Zhou S. et al, 2021 ; Fan et al, 2022 ; Lang et al, 2022 ). The other four lncRNAs, namely JHDM1D antisense 1 (JHDM1D-AS1), myocardial infarction associated transcript 2 (Mirt2), small nucleolar RNA host gene 12 (SNHG12), and PART1, exhibited anti-oxidant and anti-inflammatory roles in models of PD, as evidenced by the decline in proinflammatory cytokines and increase in SOD contents (Han et al, 2019 ; Shen et al, 2021b ; Wang C. et al, 2021 ; Yan et al, 2021 ).…”