Neurochemical Research ( IF 3.7 ) Pub Date : 2021-08-18 , DOI: 10.1007/s11064-021-03424-9 Pengfei Gao 1 , Xin Zeng 2 , Lin Zhang 2 , Long Wang 2 , Lu-Lu Shen 3 , Ya-Yun Hou 4 , Fang Zhou 2 , Xianlong Zhang 1
In numerous studies, microRNAs (miRNAs) have been authenticated to play vital roles in the pathophysiology of neuropathic pain and other neurological diseases. In our study, we focused on evaluating miR-378 and its potential effects in neuropathic pain development, as well as the underlying molecular mechanisms. Primarily, a chronic sciatic nerve injury (CCI) rat model was established. Next, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression levels of miR-378 and EZH2 mRNA; the EZH2 protein expression levels were detected by western blot. A luciferase activity assay monitored the interaction of miR-378 and EZH2. Mechanical and thermal hyperalgesia was also performed to quantitate the effects of overexpression of miR-378 or EZH2 on the CCI rats. We found that miR-378 was down-regulated in the CCI rats, and the overexpression of miR-378 produced significant relief in their pain management. EZH2 was the downstream gene of miR-378 and was negatively regulated by miR-378. The up-regulation of EZH2 reduced the inhibitory effects of miR-378 on the development of neuropathic pain in the CCI rats. miR-378 acts as an inhibitor in the progression of neuropathic pain via targeting EZH2; the miR-378/EZH2 axis may be a novel target for the diagnosis and therapy of neuropathic pain in clinical treatment.
中文翻译:
miR-378 的过表达通过靶向 EZH2 减轻慢性坐骨神经损伤
在众多研究中,microRNA (miRNA) 已被证实在神经性疼痛和其他神经系统疾病的病理生理学中发挥重要作用。在我们的研究中,我们专注于评估 miR-378 及其在神经性疼痛发展中的潜在影响,以及潜在的分子机制。首先,建立慢性坐骨神经损伤(CCI)大鼠模型。接下来,采用逆转录定量聚合酶链反应(RT-qPCR)测量miR-378和EZH2 mRNA的表达水平;Western blot检测EZH2蛋白表达水平。荧光素酶活性测定监测 miR-378 和 EZH2 的相互作用。还进行了机械和热痛觉过敏以量化 miR-378 或 EZH2 过表达对 CCI 大鼠的影响。我们发现 miR-378 在 CCI 大鼠中下调,并且 miR-378 的过表达在其疼痛管理中产生显着缓解。EZH2是miR-378的下游基因,受miR-378的负调控。EZH2的上调降低了miR-378对CCI大鼠神经性疼痛发展的抑制作用。miR-378 通过靶向 EZH2 作为神经性疼痛进展的抑制剂;miR-378/EZH2轴可能是临床治疗中神经性疼痛诊断和治疗的新靶点。miR-378 通过靶向 EZH2 作为神经性疼痛进展的抑制剂;miR-378/EZH2轴可能是临床治疗中神经性疼痛诊断和治疗的新靶点。miR-378 通过靶向 EZH2 作为神经性疼痛进展的抑制剂;miR-378/EZH2轴可能是临床治疗中神经性疼痛诊断和治疗的新靶点。