Circular RNA Related to the Chondrocyte ECM Regulates MMP13 Expression by Functioning as a MiR-136 'Sponge' in Human Cartilage Degradation.
Circular RNA Related to the Chondrocyte ECM Regulates MMP13 Expression by Functioning as a MiR-136 'Sponge' in Human Cartilage Degradation.
复制标题
与软骨细胞 ECM 相关的环状 RNA 通过在人类软骨退化中充当 MiR-136“海绵”来调节 MMP13 表达
DOI：
10.1038/srep22572
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发表时间：
2016-03-02
影响因子：
4.6
通讯作者：
Ao Y
中科院分区：
文献类型：
--
作者：
Liu Q;Zhang X;Hu X;Dai L;Fu X;Zhang J;Ao Y
环状RNA（circRNA）参与多种疾病的发生发展，但人们对circRNA在骨关节炎（OA）中的作用知之甚少。研究的目的是鉴定关节软骨中的circRNA表达，并探讨软骨细胞外基质（ECM）相关的circRNA（circRNA-CER）在软骨中的功能。为了鉴定在软骨中特异性表达的 circRNA，我们比较了 OA 软骨中的 circRNA 与正常软骨中的表达。采用生物信息学来预测软骨中 circRNA 和 mRNA 的相互作用。 circRNA-CER 的功能丧失和挽救实验在体外进行。共有 71 个 circRNA 在 OA 和正常软骨中差异表达。软骨细胞中 CircRNA-CER 的表达随着白细胞介素 1 和肿瘤坏死因子水平的增加而增加。使用小干扰 RNA 沉默 circRNA-CER 可抑制 MMP13 表达并增加 ECM 形成。 CircRNA-CER 可以与 MMP13 竞争 miR-136。我们的结果表明，circRNA-CER 通过作为竞争性内源 RNA (ceRNA) 调节 MMP13 表达，并参与软骨细胞 ECM 降解过程。我们建议 circRNA-CER 可作为 OA 治疗的潜在靶点。
Circular RNAs (circRNAs) are involved in the development of various diseases, but there is little knowledge of circRNAs in osteoarthritis (OA). The aim of study was to identify circRNA expression in articular cartilage and to explore the function of chondrocyte extracellular matrix (ECM)-related circRNAs (circRNA-CER) in cartilage. To identify circRNAs that are specifically expressed in cartilage, we compared the expression of circRNAs in OA cartilage with that in normal cartilage. Bioinformatics was employed to predict the interaction of circRNAs and mRNAs in cartilage. Loss-of-function and rescue experiments for circRNA-CER were performed in vitro. A total of 71 circRNAs were differentially expressed in OA and normal cartilage. CircRNA-CER expression increased with interleukin-1 and tumor necrosis factor levels in chondrocytes. Silencing of circRNA-CER using small interfering RNA suppressed MMP13 expression and increased ECM formation. CircRNA-CER could compete for miR-136 with MMP13. Our results demonstrated that circRNA-CER regulated MMP13 expression by functioning as a competing endogenous RNA (ceRNA) and participated in the process of chondrocyte ECM degradation. We propose that circRNA-CER could be used as a potential target in OA therapy.