Department of Spinal Surgery, Luoyang Orthopedic Hospital of Henan Province, Luoyang Henan, P.R. China.
Faculty of Graduate Studies, Tianjin University of Traditional Chinese Medicine, Tianjin P.R. China.
Cell Cycle. 2021 Sep;20(18):1828-1844. doi: 10.1080/15384101.2021.1962634. Epub 2021 Aug 10.
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.
作为最严重的神经损伤之一，脊髓损伤（SCI）导致持续的运动功能障碍，并涉及大量基因改变。需要阐明环状 RNA（circRNA）在 SCI 后神经恢复中的作用。在目前的工作中，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 数据库，评估了 circTYW1、microRNA-380（miR-380）和 FGF9 在 SCI 和假手术大鼠中的表达。制备氧葡萄糖剥夺（OGD）处理后的 PC12 细胞以模拟 SCI 模型。在 SCI 大鼠的脊髓组织中，circTYW1 表达降低，而 miR-380 表达升高，FGF9 表达降低。circTYW1 促进 SCI 大鼠的神经恢复并抑制脊髓组织中的细胞凋亡。在暴露于 OGD 的 PC12 细胞中，circTYW1 抑制 PC12 细胞凋亡；然而，miR-380 的过表达逆转了 circTYW1 对 PC12 细胞的保护作用。此外，circTYW1 通过竞争性结合 miR-380 促进 FGF9 表达，从而激活 ERK1/2 信号通路。总之，我们的结果表明，circTYW1 的减少通过调节 miR-380/FGF9/ERK1/2 轴阻止 SCI 大鼠的神经恢复，这可能为 SCI 治疗提供新的认识。
