Department of Orthopaedics, Gongli Hospital of Pudong New Area, Shanghai, China.
Gen Physiol Biophys. 2024 Sep;43(5):435-443. doi: 10.4149/gpb_2024024.
MicroRNAs (miRNAs) are essential modulators of gene expression and are associated with various pathological processes, including spinal cord injury (SCI). This investigation aimed to elucidate miR-10a activity in SCI and its potential interaction with sirtuin 1 (SIRT1). The SCI rat model was established to assess hind limb movement, measure levels of miR-10a, SIRT1, neuronal survival, and inflammatory factors. An in-vitro SCI cell model was also developed to evaluate cell viability and inflammatory factor levels. The interaction between miR10a and SIRT1 was verified. Upregulated miR-10a and downregulated SIRT1 expression were found in the tissues of SCI rats. miR-10a knockdown in SCI rats enhanced the recovery of motor function, increased neuronal survival, and reduced the levels of inflammatory cytokines. Luciferase reporter assays confirmed that miR-10a targeted SIRT1 directly. In PC12 cells, downregulation of miR-10a increased SIRT1 expression, enhanced cell viability, and reduced inflammatory factor levels after LPS stimulation. Conversely, SIRT1 knockdown inhibited the protective effects of downregulated miR-10a on cell viability and inflammatory responses. The results suggest that miR-10a downregulation protects against SCI by upregulating SIRT1 expression, improving functional recovery, and reducing inflammation. Targeting the miR-10a/SIRT1 axis is a promising strategy for SCI treatment.
微小 RNA（miRNA）是基因表达的重要调节剂，与多种病理过程有关，包括脊髓损伤（SCI）。本研究旨在阐明 miR-10a 在 SCI 中的活性及其与沉默信息调节因子 1（SIRT1）的潜在相互作用。建立 SCI 大鼠模型以评估后肢运动，测量 miR-10a、SIRT1、神经元存活和炎症因子的水平。还建立了体外 SCI 细胞模型，以评估细胞活力和炎症因子水平。验证了 miR10a 和 SIRT1 之间的相互作用。在 SCI 大鼠的组织中发现 miR-10a 上调和 SIRT1 下调表达。在 SCI 大鼠中敲低 miR-10a 可增强运动功能的恢复，增加神经元存活，并降低炎症细胞因子的水平。荧光素酶报告基因检测证实 miR-10a 可直接靶向 SIRT1。在 PC12 细胞中，下调 miR-10a 可增加 SIRT1 表达，增强细胞活力，并降低 LPS 刺激后的炎症因子水平。相反，SIRT1 敲低抑制了下调 miR-10a 对细胞活力和炎症反应的保护作用。结果表明，下调 miR-10a 通过上调 SIRT1 表达来保护 SCI，改善功能恢复并减轻炎症。靶向 miR-10a/SIRT1 轴可能是 SCI 治疗的一种有前途的策略。
