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LncRNA NEAT1 Regulates the Development of Parkinson’s Disease by Targeting AXIN1 Via Sponging miR-212-3p

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Abstract

Long non-coding RNA (lncRNA) nuclear-enriched assembly transcript 1 (NEAT1) has been reported to be highly expressed in Parkinson’s disease (PD). However, the mechanism of NEAT1 in PD progression has not been fully elucidated. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine injection (MPTP) was used to construct PD mouse models in vivo, and 1-methyl-4-phenyl pyridine (MPP+) was used to build PD cell models in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to test the expression of NEAT1, microRNA (miR)-212-3p and axis inhibition protein 1 (AXIN1). The viability, apoptosis and inflammation of cells were determined using cell counting kit 8 (CCK8) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Then, the protein levels of apoptosis-related markers and AXIN1 were measured by western blot (WB) analysis. Furthermore, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the interaction between miR-212-3p and NEAT1 or AXIN1. NEAT1 was upregulated in PD mouse models and cell models. Function experiments confirmed that NEAT1 knockdown could promote the viability, suppress the apoptosis and inflammation of MPP+-stimulated SK-N-SH cells to restrain PD progression. MiR-212-3p was downregulated in PD, and its inhibitor could reverse the suppression effect of NEAT1 knockdown on PD progression. Additionally, AXIN1 was a target of miR-212-3p, and its overexpression could invert the inhibition effect of miR-212-3p mimic on PD progression. Furthermore, AXIN1 expression was inhibited by NEAT1 silencing and promoted by NEAT1 overexpression, while these effect could be recovered by miR-212-3p inhibitor and mimic, respectively. Our results demonstrated that NEAT1 knockdown suppressed PD progression through regulating the miR-212-3p/AXIN1 pathway, indicating that NEAT1 might be a therapeutic target for neuroprotection in PD.

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  1. Tao Liu and Yang Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Tianjin Hospital of ITCWM Nankai Hospital, No. 6 Changjiang Road, Nankai District, Tianjin, 300100, China

    Tao Liu

  2. Department of Acupuncture & Physiotherapy, Tianjin Hospital of ITCWM Nankai Hospital, Tianjin, 300100, China

    Yang Zhang & Jinsheng Zhao

  3. Department of Traditional Chinese Medicine, Tianjin Fourth Central Hospital, Tianjin, 300140, China

    Weihong Liu

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  1. Tao Liu
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  2. Yang Zhang
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  4. Jinsheng Zhao
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Correspondence to Tao Liu.

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Liu, T., Zhang, Y., Liu, W. et al. LncRNA NEAT1 Regulates the Development of Parkinson’s Disease by Targeting AXIN1 Via Sponging miR-212-3p. Neurochem Res 46, 230–240 (2021). https://doi.org/10.1007/s11064-020-03157-1

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  • DOI: https://doi.org/10.1007/s11064-020-03157-1

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