CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis
CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis
复制标题
CircERCC2 通过 miR-182-5p/SIRT1 轴调节线粒体自噬和细胞凋亡，改善椎间盘退变
DOI：
10.1038/s41419-019-1978-2
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发表时间：
2019-10-03
影响因子：
9
通讯作者：
Jiang, Jianyuan
中科院分区：
文献类型：
--
作者：
Xie, Lin;Huang, Weibo;Jiang, Jianyuan
椎间盘退变（IVDD）的分子机制仍不清楚。本研究旨在探讨环状RNA（circRNA）在IVDD发病机制中的作用。我们使用患者的髓核（NP）组织、叔丁基过氧化氢（TBHP）刺激的NP细胞（NPC）和IVDD大鼠模型来探讨circERCC2与miR-182-5p/SIRT1轴之间的相互作用。结果表明，circERCC2 的下调会增加体内退行性 NP 组织以及体外 TBHP 刺激的 NPC 中 miR-182-5p 的水平并降低 SIRT1 的水平。 SIRT1-si 的治疗可激活细胞凋亡并抑制线粒体自噬。此外，miR-182-5p-si可以通过靶向SIRT1来调节NPC的线粒体自噬和凋亡。 circERCC2对NPC和IVDD大鼠模型的影响是由miR-182-5p/SIRT1轴介导的。总之，本研究首次证明circERCC2可以通过miR-182-5p/SIRT1轴激活线粒体自噬并抑制细胞凋亡来改善IVDD，并表明circERCC2是IVDD的潜在有效治疗靶点。
The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction betweencircERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation ofcircERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects ofcircERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence thatcircERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests thatcircERCC2 is a potentially effective therapeutic target for IVDD.