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LncRNA HOTAIR Promotes Neuronal Damage Through Facilitating NLRP3 Mediated-Pyroptosis Activation in Parkinson’s Disease via Regulation of miR-326/ELAVL1 Axis

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Abstract

Parkinson’s disease (PD) seriously threatens human’s health. Researches have shown a close correlation between long non-coding RNAs (lncRNAs) and PD. However, the biological function of lncRNA homeobox transcript antisense RNA (HOTAIR) in PD remains largely unknown. In this study, we established PD models in vivo and in vitro by using 1-methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) to assess the role of HOTAIR in pyroptotic cell death and neuronal damage. RNA immunoprecipitation (RIP) and dual luciferase reporter assay were used to verify the interaction between miR-326 and HOTAIR or ELAV like RNA binding protein 1 (ELAVL1). LncRNA HOTAIR was upregulated in PD mice and MPP+ induced SH-SY5Y cells. Additionally, knockdown of HOTAIR notably attenuated the symptom of PD in vivo. Downregulation of HOTAIR could obviously promoted cell viability and suppressed NLR family pyrin domain containing 3 (NLRP3) mediated pyroptotic cell death of SH-SY5Y cells in the presence of MPP+. Further, lncRNA HOTAIR positively regulated ELAVL1 expression by targeting miR-326, and downregulation of HOTAIR or ELAVL1 notably suppressed promotive effects of miR-326 inhibitor on MPP+ induced pyroptosis via activation of NLRP3 inflammasome. Collectively, HOTAIR silencing significantly inhibits neuronal damage through repressing NLRP3 mediated pyroptosis activation via regulation of miR-326/ELAVL1 axis in PD, which may contribute to a better understanding of PD pathogenesis and provide new treatment strategies for this disease.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by Natural Science Foundation of China (No. 81560201) and Doctor Foundation of Guizhou Provincial People's Hospital (No. GZSYBS [2015]03).

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Authors and Affiliations

  1. Department of Emergency, Guizhou Province, Guizhou Provincial People’s Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China

    Qian Zhang, Xiao-Mo Huang, Jian-Xiong Liao, Yu-Kang Dong, Jiang-Lan Zhu, Cun-Cun He, Jia Huang, Yao-Wei Tang, Dan Wu & Jin-Yong Tian

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  1. Qian Zhang
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Contributions

Guarantor of integrity of the entire study: J-YT, JH, C-CH, QZ, X-MH; study concepts: J-YT, QZ, JH, C-CH; study design: J-YT, J.-LZ, Y-KD; definition of intellectual content: J-YT, JH, Y-WT; literature research: J-YT, J.-LZ, C-CH, J-XL, DW; clinical studies: J-YT, QZ, JH, Y-KD; experimental studies: J-YT, J.-LZ, Y-KD; data acquisition: J-YT, JH, J-XL, DW; data analysis: J-YT, J.-LZ, J-XL, DW; statistical analysis: J-YT, QZ, JH, Y-KD; manuscript preparation: J-YT, JH, QZ, DW; manuscript editing: J-YT, JH, J-XL, DW; manuscript review: J-YT, J.-LZ, QZ, DW.

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Correspondence to Jin-Yong Tian.

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This study was approved by the Medical Ethics Committee of Guizhou Provincial People’s Hospital. The animal experiments were strictly complied with the principle to minimize the pain and suffering to experimental animals.

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Zhang, Q., Huang, XM., Liao, JX. et al. LncRNA HOTAIR Promotes Neuronal Damage Through Facilitating NLRP3 Mediated-Pyroptosis Activation in Parkinson’s Disease via Regulation of miR-326/ELAVL1 Axis. Cell Mol Neurobiol 41, 1773–1786 (2021). https://doi.org/10.1007/s10571-020-00946-8

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