Knockdown of SNHG14 Alleviates MPP+-Induced Injury in the Cell Model of Parkinson’s Disease by Targeting the miR-214-3p/KLF4 Axis

Abstract

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) has been demonstrated as an important regulator in PD pathology. However, the functional mechanisms played by SNHG14 in PD remain largely unclear. Methods: We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1methyl-4-phenylpyridinium (MPP +) to establish PD mouse and cell models. The levels of SNHG14, miR-214-3p, and Krüppel-like factor 4 (KLF4) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot analysis. Cell viability and apoptosis were determined using the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of inflammatory cytokines were evaluated by ELISA. The relationships among SNHG14, miR-214-3p, and KLF4 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: Our data indicated that SNHG14 was upregulated and miR-214-3p was downregulated in PD models. SNHG14 knockdown ameliorated MPP +-stimulated damage in SK-N-SH cells, as evidenced by the enhancement in cell viability and the suppression in cell apoptosis and pro-inflammatory cytokine production. Mechanistically, SNHG14 directly targeted miR-214-3p via binding to miR-214-3p, and SNHG14 knockdown protected SK-N-SH cell from MPP +-stimulated cytotoxicity by upregulating miR-214-3p. KLF4 was a direct target of miR-214-3p, and SNHG14 regulated KLF4 expression by acting as a miR-214-3p sponge. Furthermore, miR-214-3p overexpression alleviated MPP +-stimulated damage in SK-N-SH cells by downregulating KLF4. Conclusion: Our current study first demonstrated the protective effect of SNHG14 knockdown on MPP +-stimulated cytotoxicity in SK-N-SH cells at least partially by targeting the miR-214-3p/KLF4 axis, illuminating a promising target for PD intervention and treatment.

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

“…SNHG14 is detected on chromosome 15q11.2 and functions as an oncogene in cancers, kidney injury, and neurodegenerative diseases such as PD and AD, working as ceRNA (Qi et al, 2017 ; Wang et al, 2018 ; Zhuang et al, 2022 ). It was proved that SNHG14 is up-regulated in two ceRNA regulatory axes, including SNHG14/miR-519a-3p/ATG10 and SNHG14/miR-214-3p/KLF4 (Zhou et al, 2020b ; Zhuang et al, 2022 ). Autophagy-related 10 (ATG10) is an E2-like enzyme involved in the autophagy (Zhang M.-Q.…”

Serum miR-214 Serves as a Biomarker for Prodromal Parkinson’s Disease

“…The overexpression of miR-214 leads to a decrease in α-synuclein expression, which is a potential mechanism that underlies the neuroprotection in Resveratrol, a potential therapeutic drug in PD treatment. Another study demonstrated that miR-214 targets KLF4 in order to alleviate 1-methyl-4-phenylpyridinium (MPP + )-triggered cytotoxicity in PD (Zhou et al, 2020).…”

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

“…The progression of PD is normally accompanied by apoptosis and inflammation of nerve cells (Bhattacharyya et al, 2021 ). Two lncRNAs, namely nuclear-enriched abundant transcript 1 (NEAT1) and SNHG gene 14 (SNHG14), were identified to accelerate this progression (Zhou S. et al, 2020 ; Liu et al, 2021 ). The main hallmark of PD is the loss of dopaminergic neurons (DAs) in the substantia nigra, which correlates with typical PD symptoms including resting tremors and bradykinesia (Xin and Liu, 2021 ).…”