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Downregulation of HOTAIR reduces neuronal pyroptosis by targeting miR-455-3p/NLRP1 axis in propofol-treated neurons in vitro

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Abstract

Propofol is one of the most common intravenous anesthetics which may cause neuronal cell death in young mice. HOX transcript antisense RNA (HOTAIR) was abnormally expressed in neurodegenerative diseases. However, the effect of HOTAIR on propofol-induced pyroptosis of neurons and related mechanisms are still unknown. In this study, propofol treatment significantly reduced neuronal the viability of neurons, and promoted the expression of inflammation-related factors. Propofol treatment also promoted neuron death and neuronal pyroptosis. All the above effects might be related to the propofol-induced overexpression of HOTAIR. Interestingly, knockdown of HOTAIR by shRNA (sh-HOTAIR) significantly inhibited neuronal pyroptosis, but increased neuronal viability. Further analysis showed that HOTAIR and Nod-like receptor protein1 (NLRP1) were the targets of miR-455-3p, respectively. Notably, propofol treatment decreased the level of miR-455-3p, while increased the level of NLRP1. In addition, sh-HOTAIR increased the level of miR-455-3p, which further inhibited the expression of NLRP1 and the activation of NLRP1 inflammasome, thereby inhibiting neuronal pyroptosis. More importantly, NLRP1 overexpression decreased neuronal viability, and reactivated NLRP1 inflammasome, thus reversing the inhibitory effect of sh-HOTAIR on pyroptosis. Our findings indicated that HOTAIR inhibited propofol-induced pyroptosis of neurons by regulating miR-455-3p/NLRP1 axis, indicating that HOTAIR may be a potential therapeutic target for propofol-induced neurotoxicity.

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu, Nanchang, 330006, Jiangxi, China

    Haixia Gong, Xianwen Wan, Yang Zhang & Sisi Liang

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  1. Haixia Gong
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  2. Xianwen Wan
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  3. Yang Zhang
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  4. Sisi Liang
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Contributions

H.G. and X.W. designed the study, supervised the data collection, analyzed the data, Y.Z. interpreted the data and prepare the manuscript for publication, S.L. supervised the data collection, analyzed the data and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

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Correspondence to Xianwen Wan.

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Ethical approval was obtained from the Ethics Committee of The First Affiliated Hospital of Nanchang University.

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Gong, H., Wan, X., Zhang, Y. et al. Downregulation of HOTAIR reduces neuronal pyroptosis by targeting miR-455-3p/NLRP1 axis in propofol-treated neurons in vitro. Neurochem Res 46, 1141–1150 (2021). https://doi.org/10.1007/s11064-021-03249-6

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  • DOI: https://doi.org/10.1007/s11064-021-03249-6

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