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miR-139-5p 通过靶向 TRAF3 减轻脊髓损伤诱导的神经细胞凋亡。

MiR-139-5p alleviates neural cell apoptosis induced by spinal cord injury through targeting TRAF3.

机构信息

Department of Rehabilitation Medicine, The Fifth Affiliated Hospital of Zhengzhou University, Z, Zhengzhou, Henan Province, 450052, PR China.

出版信息

Acta Biochim Pol. 2020 Aug 27;67(3):359-365. doi: 10.18388/abp.2020_5198.

Abstract

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.

摘要

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。

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