Department of Spinal Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, China.
Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3649-3655. doi: 10.26355/eurrev_201806_15242.
To explore the role of microRNA-409 in spinal cord injury (SCI) recovery and its underlying mechanism.
The mouse SCI model was first established, and the difference in recovery of grip strength was detected. MicroRNA-409 expressions in mice tissues from sham operation group and SCI group were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). We further increased microRNA-409 level in mice spinal cord by plasmids transfection. Luciferase activity was detected to verify the direct binding of microRNA-409 and ZNF366.
The grip strength in both groups was temporarily decreased after surgery, while the grip strength in SCI group was always remarkably lower than that of the sham operation group since the first week after the surgery, suggesting the successful construction of mouse SCI model. MicroRNA-409 expression in the SCI group was gradually decreased from the postoperative 3rd day, which was remarkably lower than that of the sham group. Additionally, ZNF366 expression in the SCI group began to increase from the first day after the surgery, which was markedly higher than that of the sham group. After injection of exogenous microRNA-409, ZNF366 expression in the SCI group showed a remarkable decrease compared to that of the sham operation group. We also confirmed that ZNF366 was the target gene of microRNA-409 by bioinformatics analysis and luciferase activity assay.
MicroRNA-409 is downregulated after spinal cord injury. Overexpression of microRNA-409 directly targets ZNF366 and promotes the recovery of spinal cord injury.
探讨 microRNA-409 在脊髓损伤(SCI)恢复中的作用及其机制。
首先建立小鼠 SCI 模型,检测握力恢复的差异。采用实时定量聚合酶链反应(qRT-PCR)检测假手术组和 SCI 组小鼠组织中 microRNA-409 的表达。进一步通过质粒转染增加小鼠脊髓中的 microRNA-409 水平。检测荧光素酶活性以验证 microRNA-409 和 ZNF366 之间的直接结合。
手术后两组握力暂时下降,但 SCI 组自手术后第一周起握力始终显著低于假手术组,提示成功构建了小鼠 SCI 模型。SCI 组 microRNA-409 表达从术后第 3 天逐渐下降,显著低于假手术组。此外,SCI 组 ZNF366 表达从手术后第一天开始增加,明显高于假手术组。注射外源性 microRNA-409 后,SCI 组 ZNF366 表达明显低于假手术组。通过生物信息学分析和荧光素酶活性测定,我们还证实 ZNF366 是 microRNA-409 的靶基因。
脊髓损伤后 microRNA-409 下调。microRNA-409 的过表达可直接靶向 ZNF366,促进脊髓损伤的恢复。