Division of Spine Surgery, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
Biochem Biophys Res Commun. 2020 Jul 23;528(2):359-367. doi: 10.1016/j.bbrc.2020.02.108. Epub 2020 Apr 2.
Spinal cord injury (SCI) is a severe disable symptom and has posed a great health threat to many people. Circ-HIPK3 has been reported to modulate the biological behavior of neuronal cells. Thence, in this study, we explored the mechanism of circ-HIPK3 in affecting functions of neuronal cell in SCI. SCI rat model was constructed to evaluate the apoptosis condition of spinal cord tissue. Meanwhile, 100 μM of CoCl was used to treat AGE1.HN and PC12 cells to induce in vitro SCI model. Functional assays were implemented to investigate the apoptosis of AGE1.HN and PC12 cells. RNase R and Act D treatment were both conducted to verify the circular character of circ-HIPK3. In this study, circ-HIPK3 was found lowly expressed in SCI rat models and AGE1.HN and PC12 cells induced by 100uM of CoCl. Meanwhile, inhibited circ-HIPK3 or overexpressed circ-HIPK3 could separately elevate or reduce the apoptosis of AGE1.HN and PC12 cells. Moreover, circ-HIPK3 was identified as the ceRNA against miR-558 to up-regulate DPYSL5. Circ-HIPK3/miR-558/DPYSL5 axis modulated the apoptosis of AGE1.HN and PC12 cells in SCI. In conclusion, circ-HIPK3 relieves the neuronal cell apoptosis through regulating miR-588/DPYSL5 axis in SCI.
脊髓损伤 (SCI) 是一种严重的致残症状，对许多人构成了巨大的健康威胁。Circ-HIPK3 已被报道调节神经元细胞的生物学行为。因此，在本研究中，我们探讨了 circ-HIPK3 影响 SCI 中神经元细胞功能的机制。构建 SCI 大鼠模型以评估脊髓组织的细胞凋亡情况。同时，用 100µM CoCl 处理 AGE1.HN 和 PC12 细胞，以诱导体外 SCI 模型。进行功能测定以研究 AGE1.HN 和 PC12 细胞的凋亡。用 RNase R 和 Act D 处理均用于验证 circ-HIPK3 的环状特征。在这项研究中，发现在 SCI 大鼠模型和用 100µM CoCl 诱导的 AGE1.HN 和 PC12 细胞中 circ-HIPK3 表达水平较低。同时，抑制 circ-HIPK3 或过表达 circ-HIPK3 分别可升高或降低 AGE1.HN 和 PC12 细胞的凋亡。此外，circ-HIPK3 被鉴定为针对 miR-558 的 ceRNA，可上调 DPYSL5。Circ-HIPK3/miR-558/DPYSL5 轴调节 SCI 中 AGE1.HN 和 PC12 细胞的凋亡。总之，circ-HIPK3 通过调节 SCI 中的 miR-558/DPYSL5 轴缓解神经元细胞凋亡。
