Department of Rehabilitation Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Z, Zhengzhou, Henan Province, 450052, PR China.
Acta Biochim Pol. 2020 Aug 27;67(3):359-365. doi: 10.18388/abp.2020_5198.
Spinal cord injury (SCI) is a neurological trauma that causes loss of locomotor function and sensory deficit. Previous studies showed that miRNAs play a crucial role in SCI. This study further evaluated the potential role of miR-139-5p in the neural cell apoptosis after SCI in rats. A rat SCI model was successfully established and miR-139-5p expression level in SCI rats was down-regulated compared to the sham group (sham operation group) determined by qRT-PCR. MiR-139-5p overexpression via administration with miR-139-5p agomir improved locomotor functional recovery, attenuated allodynia and hyperalgesia and alleviated neural cell apoptosis in SCI rats. In addition, TRAF3 (TNF receptor-associated factor 3 ) was identified to be a target of miR-139-5p by searching the proposed target genes in TargetScan 7.1 database. Co-transfection of miR-139-5p agomir and adenovirus of TRAF3 plasmids significantly improved functional recovery and alleviated neural cell apoptosis. Therefore, TRAF3 mediated the anti-apoptosis effect of miR-139-5p in SCI rats and miR-139-5p could be a promising candidate for SCI therapy by alleviating neural cell apoptosis through targeting TRAF3.
脊髓损伤(SCI)是一种神经系统创伤,会导致运动功能丧失和感觉缺陷。先前的研究表明,miRNA 在 SCI 中发挥着至关重要的作用。本研究进一步评估了 miR-139-5p 在大鼠 SCI 后神经细胞凋亡中的潜在作用。成功建立了大鼠 SCI 模型,并通过 qRT-PCR 确定与假手术组(假手术组)相比,SCI 大鼠中 miR-139-5p 的表达水平下调。通过给予 miR-139-5p 激动剂来上调 miR-139-5p,可改善大鼠的运动功能恢复,减轻痛觉过敏和痛觉超敏,并减轻 SCI 大鼠的神经细胞凋亡。此外,通过在 TargetScan 7.1 数据库中搜索预测的靶基因,鉴定出 TRAF3(TNF 受体相关因子 3)是 miR-139-5p 的靶基因。共转染 miR-139-5p 激动剂和 TRAF3 质粒的腺病毒显著改善了功能恢复并减轻了神经细胞凋亡。因此,TRAF3 介导了 miR-139-5p 在 SCI 大鼠中的抗凋亡作用,并且 miR-139-5p 可以通过靶向 TRAF3 减轻神经细胞凋亡,成为 SCI 治疗的有前途的候选药物。