VIRMA promotes neuron apoptosis via inducing m6A methylation of STK10 in spinal cord injury animal models

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2023-09-18 DOI:10.1111/cns.14453

Hongxiang Hong, Guanhua Xu, Guofeng Bao, Jinlong Zhang, Chu Chen, Jiajia Chen, Chunshuai Wu, Jiawei Jiang, Jiayi Huang, Haiming Huang, Zhiming Cui

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Abstract

Background

Spinal cord injury (SCI) occurs as a devastating neuropathic disease. The role of serine–threonine kinase 10 (STK10) in the development of SCI remains unclear.

Objective

This study aimed to investigate the action of m6A methylation on STK10 in the apoptosis of spinal cord neurons in the pathogenesis of SCI and the possible underlying mechanisms.

Methods

Rat model of SCI was established and subsequently evaluated for motor function, pathological conditions, and apoptosis of spinal cord neurons. And the effects of overexpression of STK10 on neuronal cells in animal models of spinal cord injury and glyoxylate deprivation (OGD) cell models were evaluated. m6A2Target database and SRAMP database were used to predict the m6A methylation sites of STK10. The methylation kits were used to detect overall m6A methylation. Finally, the interaction between STK10 and vir like m6A methyltransferase associated (VIRMA) was explored in animal and cellular models.

Results

STK10 is markedly decreased in spinal cord injury models and overexpression of STK10 inhibits neuronal apoptosis. VIRMA can induce m6A methylation of STK10. VIRMA is over-expressed in spinal cord injury models and negatively regulates the expression of STK10. m6A methylation and apoptosis of neuronal cells are reduced by the knockdown of VIRMA and STK10 shRNA have shown the opposite effects.

Conclusions

VIRMA promotes neuronal apoptosis in spinal cord injury by regulating STK10 m6A methylation.

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在脊髓损伤动物模型中，VIRMA 通过诱导 STK10 的 m6A 甲基化促进神经元凋亡。

背景：脊髓损伤（SCI）是一种破坏性神经病变。丝氨酸-苏氨酸激酶 10（STK10）在 SCI 发病中的作用仍不清楚：本研究旨在探讨 STK10 的 m6A 甲基化在 SCI 发病过程中对脊髓神经元凋亡的作用及其可能的内在机制：方法：建立 SCI 大鼠模型，并对其运动功能、病理状况和脊髓神经元凋亡进行评估。利用 m6A2Target 数据库和 SRAMP 数据库预测 STK10 的 m6A 甲基化位点。甲基化试剂盒用于检测整体 m6A 甲基化。最后，在动物和细胞模型中探讨了 STK10 与病毒样 m6A 甲基转移酶相关（VIRMA）之间的相互作用：结果：STK10 在脊髓损伤模型中明显减少，过表达 STK10 可抑制神经元凋亡。VIRMA 可诱导 STK10 的 m6A 甲基化。VIRMA在脊髓损伤模型中过度表达，并负向调节STK10的表达。敲除VIRMA可减少神经元细胞的m6A甲基化和凋亡，而STK10 shRNA则显示出相反的效果：结论：VIRMA通过调节STK10 m6A甲基化促进脊髓损伤中神经元的凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.