CircSNHG5 Sponges Mir-495-3p and Modulates CITED2 to Protect Cartilage Endplate From Degradation.
CircSNHG5 Sponges Mir-495-3p and Modulates CITED2 to Protect Cartilage Endplate From Degradation.
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CircSNHG5 海绵 Mir-495-3p 并调节 CITED2 以保护软骨终板免遭降解。
DOI：
10.3389/fcell.2021.668715
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发表时间：
2021
影响因子：
5.5
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Zhang J;Hu S;Ding R;Yuan J;Jia J;Wu T;Cheng X
椎间盘退变（IDD）是一种高度流行的退行性疾病，产生大量的下背部和颈部疼痛。软骨终板（CEP）在生理和病理条件下对椎间盘至关重要。此外，环状RNA（circRNA）已被证明参与各种疾病的调节，包括IDD。然而，circRNA在颈椎CEP退变中的特殊作用仍不清楚。在这里，我们研究了circRNA在颈椎骨折和退行性颈椎病（DCM）患者CEP中的独特作用。在前人研究的基础上，建立了人竞争性内源性RNA（ceRNA）芯片。采用免疫印迹（WB）、免疫荧光（IF）、定量RT-PCR（qRT-PCR）、荧光素酶试验和荧光原位杂交（FISH）分析circSNHG 5及其下游效应子miR-495- 3 p和CITED 2的功能。我们证明，circSNHG 5的表达在退行性CEP组织中基本上是低的。软骨细胞中circSNHG 5的敲低导致细胞增殖的损失，随后是细胞外基质（ECM）的降解。此外，circSNHG 5显示海绵miR-495- 3 p和调节下游基因CITED 2的表达。这种作用机制通过CITED 2的过表达和敲低得到进一步验证。我们的研究结果发现了一种新的负责IDD进展的circSNHG 5-miR-495- 3 p轴。未来对IDD治疗的研究可能会受益于靶向这一轴。
Intervertebral disc degeneration (IDD) is a highly prevalent degenerating disease that produces tremendous amount of low back and neck pain. The cartilage endplate (CEP) is vitally important to intervertebral discs in both physiological and pathological conditions. In addition, circular RNAs (circRNAs) have been shown to be involved in the regulation of various diseases, including IDD. However, the particular role of circRNAs in cervical vertebral CEP degeneration remains unclear. Here, we examined the unique role of circRNAs in CEP of patients with cervical fracture and degenerative cervical myelopathy (DCM). Human competitive endogenous RNA (ceRNA) microarray was performed by previous research. Western blot (WB), immunofluorescence (IF), quantitative RT-PCR (qRT-PCR), luciferase assay, and fluorescence in situ hybridization (FISH) were employed to analyze the function of circSNHG5 and its downstream effectors, miR-495-3p, and CITED2. We demonstrated that circSNHG5 expression was substantially low in degenerative CEP tissues. Knockdown of circSNHG5 in chondrocytes resulted in a loss of cell proliferation and followed by degradation of extracellular matrix (ECM). In addition, circSNHG5 was shown to sponge miR-495-3p and modulate the expression of the downstream gene CITED2. This mechanism of action was further validated via overexpression and knockdown of CITED2. Our findings identified a novel circSNHG5-miR-495-3p axis responsible for IDD progression. Future investigations into IDD therapy may benefit from targeting this axis.
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影响因子：
37.3
作者：
Chen LY;Wang L;Ren YX;Pang Z;Liu Y;Sun XD;Tu J;Zhi Z;Qin Y;Sun LN;Li JM
通讯作者：
Li JM
影响因子：
37.3
作者：
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通讯作者：
Wu Y
影响因子：
5.3
作者：
Grunhagen, T;Wilde, G;Urban, JPG
通讯作者：
Urban, JPG
影响因子：
28.5
作者：
Sanchez-Mejias A;Tay Y
通讯作者：
Tay Y
影响因子：
5.2
作者：
He, Zhiyong;Leong, Daniel J.;Sun, Hui B.
通讯作者：
Sun, Hui B.