Dopaminergic Neuron Injury in Parkinson Disease Is Mitigated by Interfering lncRNA SNHG14 Expression to Regulate the miR-133b/α-Synuclein Pathway

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Background: Abundant α-synuclein (α-syn) protein accumulation is the pathological hallmark of Parkinson disease (PD) and it induces dopaminergic (DA) neuron apoptosis. This study explored the influence of long non-coding RNA (lncRNA) SNHG14 on α-syn expression and PD pathogenesis. Methods: PD model was established in mouse with a stereotaxic surgery. In the brain tissue of PD mice, the expression levels of SNHG14, miR-133b, α-syn and SP-1 protein were determined. Chromatin immunoprecipitation (ChIP) assay was performed to validate the binding between SP-1 and SNHG14 promoter. DA neuron viability was analyzed with CCk-8 assay. Interplay between SNHG14 and miR-133b was examined with RNA immunoprecipitation (RIP) and RNA pull-down assay. Regulatory relationship between miR-133b and α-syn was verified through dual luciferase reporter assay. Results: Compared with the sham group (n=7), the expression of SNHG14, αsyn and SP-1 protein was increased in PD mice model (n=7), while miR-133b was down-regulated. Binding between transcriptional factor SP-1 and SNHG14 promoter was enhanced by rotenone, and promoted SNHG14 expression. Interference of SNHG14 ameliorated the DA neuron injury induced by rotenone. Interaction between SNHG14 and miR-133b was identified in clonal mesencephalic DA cell line MN9D cells. MiR-133b negatively regulated α-syn expression by targeting its 3'-UTR of mRNA. SNHG14 regulated α-syn expression via targeting miR-133b. Interference of SNHG14 improved DA neuron activity that damaged by rotenone through miR-133b. Interference of SNHG14 mitigated neuron injury in PD mouse model. Conclusion: Interference of lncRNA SNHG14 expression mitigates dopaminergic neuron injury by down-regulating α-syn via targeting miR133b, which contributes to improving PD pathological state. Funding Statement: This study was supported by the grants from the Youth Entrepreneurship Foundation of the First Affiliated Hospital of Zhengzhou University. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All animal experiments were approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.