Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein.
Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein.
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环状RNA VMA21通过靶向miR-200c和X连锁凋亡抑制剂蛋白来防止椎间盘退变
DOI：
10.1136/annrheumdis-2017-212056
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发表时间：
2018-05
影响因子：
27.4
通讯作者：
Zhao J
中科院分区：
文献类型：
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作者：
Cheng X;Zhang L;Zhang K;Zhang G;Hu Y;Sun X;Zhao C;Li H;Li YM;Zhao J
目的研究表明，CircRNAs(CircRNAs)作为竞争内源性RNAs与microRNAs(MiRNAs)相互作用，影响miRNA靶向mRNAs的表达。在这项研究中，我们研究了CircRNAs是否可以作为竞争内源性RNAs来调节椎间盘退变(IVDD)的病理过程。方法在患者和大鼠模型的髓核(NP)细胞和退变的NP组织中，探讨CircRNA CircVMA21在IVDD中的作用和机制。检测了CircVMA21与miR-200C以及靶基因X连锁的凋亡抑制蛋白(XIAP)之间的相互作用。结果炎性细胞因子处理的NP细胞和退变的NP组织中XIAP的表达下降与细胞外基质的过度凋亡和细胞外基质中合成和分解代谢因子的失衡直接相关。MIR-200C通过抑制XIAP来调节NP细胞的活性和功能。CircVMA21作为miR-200C的海绵，通过靶向miR-200C和XIAP在NP细胞中发挥作用。椎管内注射CircVMA21可减轻模型大鼠的IVDD。结论CircVMA21可通过miR-200C-XIAP途径减轻炎性细胞因子诱导的NP细胞凋亡和细胞外基质合成/分解代谢失衡。它为IVDD提供了一种潜在有效的治疗策略。
Objectives Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD). Methods The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined. Results The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model. Conclusions CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.
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影响因子：
4.9
作者：
Le Maitre, Christine Lyn;Hoyland, Judith Alison;Freemont, Anthony J
通讯作者：
Freemont, Anthony J
影响因子：
7
作者：
Phillips, K. L. E.;Cullen, K.;Le Maitre, C. L.
通讯作者：
Le Maitre, C. L.
影响因子：
4.8
作者：
Eckelman, BP;Salvesen, GS
通讯作者：
Salvesen, GS
DOI：
10.1038/nrrheum.2013.160
发表时间：
2014-01
期刊：
Nature reviews. Rheumatology
影响因子：
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作者：
通讯作者：
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影响因子：
168.9
作者：
通讯作者：
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