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The Effect of SPTLC2 on Promoting Neuronal Apoptosis is Alleviated by MiR-124-3p Through TLR4 Signalling Pathway

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Abstract

To investigate the role and mechanism of microRNA-124-3p (miR-124-3p) and serine palmitoyltransferase long chain base subunit 2 (SPTLC2) in neuronal apoptosis induced by mechanical injury. Transient transfection was used to modify the expression of miR-124-3p and SPTLC2. After transfection, neuronal apoptosis was evaluated in an in vitro injury model of primary neurons using TUNEL staining and western blot. The correlation between miR-124-3p and SPTLC2 was identified through a dual luciferase reporter assay in HEK293 cells. A rescue experiment in primary neurons was performed to further confirm the result. To explore the downstream mechanisms, co-immunoprecipitation was performed to identify proteins that interact with SPTLC2 in toll-like receptor 4 (TLR4) signalling pathway. Subsequently, the relative expression levels of TLR4 pathway molecules were measured by western blot. Our results showed that increased miR-124-3p can inhibit neuronal apoptosis, which is opposite to the effect of SPTLC2. In addition, miR-124-3p was proved to negatively regulate SPTLC2 expression and suppress the apoptosis-promoting effect of SPTLC2 via the TLR4 signalling pathway.

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Funding

This study was supported by the Natural Science Foundation of China (No. 81471264).

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Author notes

  1. Xinhong Su and Yuqin Ye have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, No. 169 Changle Western Road, Xi’an, 710032, Shanxi, China

    Xinhong Su, Yongxiang Yang, Wei Bai, Huijun Chen, Enming Kang, Chuiguang Kong & Xiaosheng He

  2. Department of Neurosurgery, PLA 921rd Hospital, Changsha, 410000, Hunan, China

    Yuqin Ye

  3. Department of Orthopedic Surgery, Orthopedic Oncology Institute of Chinese PLA, Tangdu Hospital, Air Force Military Medical University, Xi’an, 710032, Shanxi, China

    Kailiang Zhang

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  1. Xinhong Su
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Su, X., Ye, Y., Yang, Y. et al. The Effect of SPTLC2 on Promoting Neuronal Apoptosis is Alleviated by MiR-124-3p Through TLR4 Signalling Pathway. Neurochem Res 44, 2113–2122 (2019). https://doi.org/10.1007/s11064-019-02849-7

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  • DOI: https://doi.org/10.1007/s11064-019-02849-7

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