Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-185-5p and matrix metalloproteinase 2
Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-185-5p and matrix metalloproteinase 2
复制标题
源自 TIMP2 的环状 RNA 作为竞争性内源性 RNA，通过靶向 miR-185-5p 和基质金属蛋白酶 2 调节椎间盘退变
DOI：
10.3892/ijmm.2020.4621
复制
发表时间：
2020-08-01
影响因子：
5.4
通讯作者：
Cui, Qing
中科院分区：
文献类型：
--
作者：
Guo, Wei;Zhang, Bin;Cui, Qing
椎间盘退变（IDD）是下背痛的一个重要原因，尽管其潜在机制仍然知之甚少。本研究的目的是研究来自金属肽酶组织抑制剂2（circ-TIMP 2）的环状RNA在退变髓核（NP）组织中的作用，并验证其在培养的人NP细胞中的功能。在NP细胞中过表达miR-185- 5 p显著抑制由肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1 β）处理诱导的增强的细胞外基质（ECM）催化。生物信息学分析表明，基质金属蛋白酶2（MMP 2）是miR-185- 5 p的潜在靶点。与未处理的细胞相比，用TNF-α和IL-1 β处理后NP细胞中的MMP 2蛋白表达水平增加，并且这种作用被miR-185- 5 p转染减弱。与正常NP组织相比，IDD样品表现出更高的circ-TIMP 2表达水平。此外，circ-TIMP 2过表达促进ECM的活化，抑制ECM的活化。此外，circ-TIMP 2隔离miR-185- 5 p，这可能潜在地上调与ECM降解相关的靶基因。总之，本研究的结果显示，circ-TIMP 2通过miR-185- 5 p-MMP 2信号传导促进TNF-α和IL-1 β诱导的NP细胞在ECM拮抗剂和催化剂之间的不平衡。这些发现为IDD的治疗提供了潜在的治疗选择。
Intervertebral disc degeneration (IDD) is an important cause of lower back pain, although the underlying mechanisms remain poorly understood. The present study aimed to examine the role of a circular RNA derived from tissue inhibitor of metallopeptidases 2 (circ-TIMP2) in degenerative nucleus pulposus (NP) tissues, and to validate its function in cultured human NP cells. Overexpression of miR-185-5p in NP cells markedly inhibited the enhanced extracellular matrix (ECM) catabolism induced by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) treatment. Bioinformatics analysis demonstrated that matrix metalloproteinase 2 (MMP2) was a potential target of miR-185-5p. MMP2 protein expression levels were increased following treatment with TNF-alpha and IL-1 beta in NP cells compared with those in untreated cells, and this effect was attenuated by transfection with miR-185-5p. Compared with normal NP tissues, IDD samples exhibited higher circ-TIMP2 expression levels. In addition, overexpres-sion of circ-TIMP2 promoted ECM catabolism and suppressed ECM anabolism. Furthermore, circ-TIMP2 sequestered miR-185-5p, which may potentially upregulate the target genes associated with ECM degradation. In conclusion, the results of the present study revealed that circ-TIMP2 promoted TNF-alpha- and IL-1 beta-induced NP cell imbalance between ECM anabolism and catabolism via miR-185-5p-MMP2 signaling. These findings provide a potential therapeutic option for the treatment of IDD.