CircTYW1 serves as a sponge for microRNA-380 in accelerating neurological recovery following spinal cord injury via regulating FGF9
CircTYW1 serves as a sponge for microRNA-380 in accelerating neurological recovery following spinal cord injury via regulating FGF9
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DOI：
10.1080/15384101.2021.1962634
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发表时间：
2021-08-12
期刊：
影响因子：
4.3
通讯作者：
Cao, Xiangyang
中科院分区：
文献类型：
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作者：
Sun, Yanpeng;Zhou, Yingjie;Cao, Xiangyang
作为最严重的神经损伤之一，脊髓损伤 (SCI) 会导致持续性运动功能障碍，并涉及大量基因改变。环状 RNA (circRNA) 在 SCI 后神经功能恢复中的参与需要澄清。在当前的工作中，我们试图评估 hsa_circRNA_0003962/circTYW1 的功能及其在 SCI 中的潜在机制。通过访问 GEO 存储库，评估了 SCI 和假手术大鼠中 circTYW1、microRNA-380 (miR-380) 和 FGF9 的表达。制备经氧糖剥夺 (OGD) 处理后的 PC12 细胞来模拟 SCI 模型。 SCI大鼠脊髓组织中circTYW1和FGF9低表达，而miR-380高表达。 circTYW1促进SCI大鼠神经功能恢复并抑制脊髓组织细胞凋亡。在暴露于 OGD 的 PC12 细胞中，circTYW1 抑制 PC12 细胞凋亡；然而，miR-380 过表达逆转了 circTYW1 对 PC12 细胞的保护作用。此外，circTYW1 通过与 miR-380 竞争性结合来促进 FGF9 表达，从而激活 ERK1/2 信号传导。总之，我们的结果表明，circTYW1的下降通过调节miR-380/FGF9/ERK1/2轴来阻止SCI大鼠的神经功能恢复，这可能为SCI治疗提供新的认识。
As one of the most severe kinds of neurological damage, spinal cord injury (SCI) contributes to persistent motor dysfunction and involves a large repertoire of gene alterations. The participation of circular RNAs (circRNAs) in neurological recovery following SCI needs to be clarified. In the current work, we attempted to assess the function of hsa_circRNA_0003962/circTYW1 and its underlying mechanism in SCI. By accessing the GEO repository, the expression of circTYW1, microRNA-380 (miR-380), and FGF9 in SCI and sham-operated rats was evaluated. PC12 cells after oxygen-glucose deprivation (OGD) treatment were prepared to mimic the SCI model. circTYW1 and FGF9 were poorly expressed, whereas miR-380 was highly expressed in the spinal cord tissues of SCI rats. circTYW1 promoted neurological recovery in SCI rats and inhibited apoptosis in spinal cord tissues. In PC12 cells exposed to OGD, circTYW1 suppressed PC12 cell apoptosis; however, miR-380 overexpression reversed the protective effect of circTYW1 on PC12 cells. Also, circTYW1 promoted FGF9 expression through competitively binding to miR-380, which activated the ERK1/2 signaling. In summary, our results demonstrated that declines in circTYW1 prevented SCI rats from neurological recovery by regulating the miR-380/FGF9/ERK1/2 axis, which might provide new understanding for SCI treatment.