Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(−/−) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(−/−) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.

目前，脊髓损伤 (SCI) 无法治愈，这对患者的生理和心理造成沉重负担。我们发现 microRNA-139-5p (miR-139-5p) 表达在小鼠受损脊髓中显着下调。因此，我们旨在测试用 miR-139-5p 治疗对 SCI 小鼠功能恢复和神经性疼痛的影响，并研究其潜在机制。荧光素酶报告基因检测显示 miR-139-5p 直接靶向哺乳动物不育 20 样激酶 1 (Mst1)，并且 miR-139-5p 处理抑制了小鼠受损脊髓中 Mst1 蛋白的表达。野生型小鼠和 Mst1(-/-) 小鼠暴露于 SCI 并通过鞘内输注用 miR-139-5p agomir 进行治疗。用 miR-139-5p 治疗 SCI 小鼠加速运动功能恢复，降低对机械和热刺激的超敏反应，并促进受损脊髓中的神经元存活。用 miR-139-5p 治疗可增强一磷酸腺苷活化蛋白激酶 α (AMPKα) 的磷酸化，改善线粒体功能，并抑制受损脊髓中与 NF-κB 相关的炎症。Mst1 的缺乏对 SCI 小鼠有类似的益处。此外，miR-139-5p 处理并未在 Mst1(-/-) 小鼠中提供进一步的保护以对抗 SCI。总之，miR-139-5p 治疗增强了 SCI 小鼠的功能恢复并降低了疼痛超敏反应，可能是通过靶向 Mst1。改善线粒体功能，并抑制受损脊髓中与 NF-κB 相关的炎症。Mst1 的缺乏对 SCI 小鼠有类似的益处。此外，miR-139-5p 处理并未在 Mst1(-/-) 小鼠中提供进一步的保护以对抗 SCI。总之，miR-139-5p 治疗增强了 SCI 小鼠的功能恢复并降低了疼痛超敏反应，可能是通过靶向 Mst1。改善线粒体功能，并抑制受损脊髓中与 NF-κB 相关的炎症。Mst1 的缺乏对 SCI 小鼠有类似的益处。此外，miR-139-5p 处理并未在 Mst1(-/-) 小鼠中提供进一步的保护以对抗 SCI。总之，miR-139-5p 治疗增强了 SCI 小鼠的功能恢复并降低了疼痛超敏反应，可能是通过靶向 Mst1。