CircCOG8 Downregulation Contributes to the Compression-Induced Intervertebral Disk Degeneration by Targeting miR-182-5p and FOXO3.
CircCOG8 Downregulation Contributes to the Compression-Induced Intervertebral Disk Degeneration by Targeting miR-182-5p and FOXO3.
复制标题
CircCOG8 下调通过靶向 miR-182-5p 和 FOXO3 导致压迫引起的椎间盘退变
DOI：
10.3389/fcell.2020.581941
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Xiang Q;Kang L;Zhao K;Wang J;Hua W;Song Y;Feng X;Li G;Lu S;Wang K;Yang C;Zhang Y
环状RNAs(CircRNAs)在人类各种疾病的发病机制中发挥着重要作用。腰椎间盘退行性变(IDD)被认为是引起下腰痛的主要原因，而机械应力是IDD的主要诱因。然而，对于CircRNAs在IDD发展过程中机械应力所起的作用知之甚少。在本研究中，我们鉴定了一种新的CircRNA，并研究了该CircRNA在压缩负荷诱导的IDD过程中的作用。我们检测了CircCOG8在机械应力作用下在视盘NP细胞中的表达模式，并观察了其功能。我们进行了生物信息学分析、RNA免疫沉淀实验和报告基因检测，以揭示CircCOG8下调介导的IVD变性的机制。结果表明，机械应力可明显下调视盘NP细胞CircCOG8的表达。CircCOG8在体外和体外均能抑制NP细胞的凋亡、细胞内ROS积聚和ECM降解。CircCOG8直接与miR-182-5p相互作用，从而调节FOXO_3的表达，从而影响压迫诱导的IDD进展。综上所述，本研究揭示了CircCOG8/miR-182-5p/FOXO_3通路是IDD进展过程中压迫的一个重要的潜在机制。CircCOG8干预治疗IDD是一种新的治疗策略。
Circular RNAs (circRNAs) have been increasingly demonstrated to play critical roles in the pathogenesis of various human diseases. Intervertebral disk degeneration (IDD) is recognized as the major contributor to lower back pain, and mechanical stress is a predominant trigger for IDD. However, little is known about the part that circRNAs play in the involvement of mechanical stress during IDD development. In the present study, we identified a novel circRNA and examined the role of this circRNA in a compression loading-induced IDD process. We detected the expression pattern of circCOG8 and observed its function in disk NP cells under mechanical stress. We conducted bioinformatics analysis, RNA immunoprecipitation experiment, and reporter gene assay to unveil the mechanism of the circCOG8 downregulation mediated IVD degeneration. Results showed that the circCOG8 expression was obviously down-regulated by the mechanical stress in disk NP cells. CircCOG8 attenuated NP cells apoptosis, intracellular ROS accumulation, and ECM degradation in vitro and ex vivo. CircCOG8 directly interacted with miR-182-5p and, thus, modulated the FOXO3 expression to affect the compression-induced IDD progression. Altogether, the present study revealed that the circCOG8/miR-182-5p/FOXO3 pathway was an important underlying mechanism in the involvement of compression during the IDD progression. Intervention of circCOG8 is a new therapeutic strategy for IDD treatment.