CircRNA-CIDN mitigated compression loading-induced damage in human nucleus pulposus cells via miR-34a-5p/SIRT1 axis
CircRNA-CIDN mitigated compression loading-induced damage in human nucleus pulposus cells via miR-34a-5p/SIRT1 axis
复制标题
CircRNA-CIDN 通过 miR-34a-5p/SIRT1 轴减轻压缩负荷诱导的人髓核细胞损伤
DOI：
10.1016/j.ebiom.2020.102679
复制
发表时间：
2020-03-01
期刊：
影响因子：
11.1
通讯作者：
Zhang, Yukun
中科院分区：
文献类型：
--
作者：
Xiang, Qian;Kang, Liang;Zhang, Yukun
工作背景：椎间盘退变（IDD）是下腰痛的主要原因，然而，IDD的分子和发病机制知之甚少。作为IDD的一个高危因素，在IDD的发展过程中，压力可诱导髓核细胞凋亡和细胞外基质降解。环状RNA（circRNA）是一类内源性非编码RNA（ncRNA），并且已被报道在多种疾病中起作用。然而，circRNA是否以及如何调节NP细胞的压缩诱导的损伤仍然是模糊的。在这里，我们的目的是调查circRNA在压缩负荷诱导IDD.Methods的关键作用：我们分析了三个样品的circRNA表达的压缩处理的NP细胞和三个对照样品，使用circRNA微阵列分析，并进一步研究了circRNA参与压缩诱导损伤的NP细胞（circRNA-CIDN）。我们在体外和离体研究了circRNA-CIDN对压缩诱导的细胞凋亡和NP ECM降解的影响。我们观察到，基于荧光素酶和RNA免疫沉淀（RIP）assays，circRNA-CIDN绑定到miRNA作为一个miRNA海绵：circRNA-CIDN是显着下调压缩处理的人NP细胞，通过circRNA微阵列和qRT-PCR分析验证，和过表达circRNA-CIDN抑制压缩诱导的细胞凋亡和NP ECM降解。进一步的研究表明，circRNA-CIDN充当miR-34 a-5 p的海绵，miR-34 a-5 p是一种重要的miRNA，通过抑制沉默的交配型信息调节2同源物1（SIRT 1）来增强NP细胞的压缩诱导的损伤。CircRNA-CIDN也被证实在离体IDD模型中包含IDD的发展。解释：我们的结果显示，circRNA-CIDN与miR-34 a-5 p的结合通过靶向SIRT 1在减轻压力负荷诱导的髓核细胞损伤中发挥重要作用，为IDD治疗提供了潜在的治疗策略。国家自然科学基金（81772391，81974348），中央高校基础研究基金（2017 KFYXJJ 248）。(c)2020作者（S）由爱思唯尔公司出版。这是一个开放获取的文章下，CC BY-NC-ND许可证。(http：//creativecommons.org/licenses/by-nc-nd/4.0/）
Background: Intervertebral disc degeneration (IDD) is a major contributor to lower back pain, however, the molecular and pathogenetic mechanisms underlying IDD are poorly understood. As a high-risk factor for IDD, compression stress was reported to induce apoptosis of nucleus pulposus (NP) cells and extracellular matrix (ECM) degradation during IDD progression. Circular RNA (circRNA) is a class of endogenous non-coding RNA (ncRNA) and has been reported to function in several diseases. However, whether and how circRNA regulates compression-induced damage of NP cells remains vague. Here, we aimed to investigate the key role of circRNA in compression loading-induced IDD.Methods: We analysed the circRNA expression of three samples from compression-treated NP cells and three control samples using circRNA microarray assays and further investigated the circRNA involved in compression-induced damage of NP cells (circRNA-CIDN). We investigated the effects of circRNA-CIDN on compression-induced cell apoptosis and NP ECM degradation in vitro and ex vivo. We observed that circRNA-CIDN bound to miRNAs as a miRNA sponge based on luciferase and RNA immunoprecipitation (RIP) assays.Findings:: CircRNA-CIDN was significantly downregulated in compression-treated human NP cells, as validated by circRNA microarray and qRT-PCR analysis, and overexpressing circRNA-CIDN inhibited compression-induced apoptosis and NP ECM degradation. Further studies demonstrated that circRNA-CIDN served as a sponge for miR-34a-5p, an important miRNA that enhanced compression-induced damage of NP cells via repressing the silent mating type information regulation 2 homolog 1 (SIRT1). CircRNA-CIDN was also verified to contain IDD development in an ex vivo IDD model.Interpretation: Our results revealed that circRNA-CIDN binding to miR-34a-5p played an important role in mitigating compression loading-induced nucleus pulposus cell damage via targeting SIRT1, providing a potential therapeutic strategy for IDD treatment.Funding: National Natural Science Foundation of China (81772391, 81974348), Fundamental Research Funds for the Central Universities (2017KFYXJJ248). (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)