Gao Gang, Duan Yufen, Chang Feng, Zhang Ting, Huang Xinhu, Yu Chen
Department of spinal minimally invasive surgery, Shanxi Provincial People's Hospital, No.29 Shuangtasi Street, Taiyuan City, Shanxi Province, 030012, China.
Department of endocrinology, Shanxi coal central hospital, No.101 Xuefu street, Xiaodian District, Taiyuan City, Shanxi Province, China.
Cell Death Discov. 2022 Jan 10;8(1):15. doi: 10.1038/s41420-021-00808-2.
Spinal cord injury (SCI) is a devastating traumatic condition. METTL14-mediated m6A modification is associated with SCI. This study was intended to investigate the functional mechanism of RNA methyltransferase METTL14 in spinal cord neuron apoptosis during SCI. The SCI rat model was established, followed by evaluation of pathological conditions, apoptosis, and viability of spinal cord neurons. The neuronal function of primary cultured spinal motoneurons of rats was assessed after hypoxia/reoxygenation treatment. Expressions of EEF1A2, Akt/mTOR pathway-related proteins, inflammatory cytokines, and apoptosis-related proteins were detected. EEF1A2 was weakly expressed and Akt/mTOR pathway was inhibited in SCI rat models. Hypoxia/Reoxygenation decreased the viability of spinal cord neurons, promoted LDH release and neuronal apoptosis. EEF1A2 overexpression promoted the viability of spinal cord neurons, inhibited neuronal apoptosis, and decreased inflammatory cytokine levels. Silencing METTL14 inhibited m6A modification of EEF1A2 and increased EEF1A2 expression while METTL14 overexpression showed reverse results. EEF1A2 overexpression promoted viability and inhibited apoptosis of spinal cord neurons and inflammation by activating the Akt/mTOR pathway. In conclusion, silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated SCI by inhibiting m6A modification of EEF1A2 and activating the Akt/mTOR pathway.
脊髓损伤（SCI）是一种毁灭性的创伤性疾病。METTL14介导的m6A修饰与SCI相关。本研究旨在探讨RNA甲基转移酶METTL14在SCI期间脊髓神经元凋亡中的功能机制。建立SCI大鼠模型，随后评估脊髓神经元的病理状况、凋亡和活力。对大鼠原代培养的脊髓运动神经元进行缺氧/复氧处理后评估其神经元功能。检测EEF1A2、Akt/mTOR通路相关蛋白、炎性细胞因子和凋亡相关蛋白的表达。在SCI大鼠模型中，EEF1A2表达较弱，Akt/mTOR通路受到抑制。缺氧/复氧降低了脊髓神经元的活力，促进了乳酸脱氢酶（LDH）释放和神经元凋亡。EEF1A2过表达促进了脊髓神经元的活力，抑制了神经元凋亡，并降低了炎性细胞因子水平。沉默METTL14抑制了EEF1A2的m6A修饰并增加了EEF1A2表达，而METTL14过表达则显示出相反的结果。EEF1A2过表达通过激活Akt/mTOR通路促进脊髓神经元的活力，抑制其凋亡和炎症。总之，沉默METTL14通过抑制EEF1A2的m6A修饰并激活Akt/mTOR通路，抑制脊髓神经元凋亡并减轻SCI。
