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Wang Jianle,Xia Dongdong,Lin Yan,Xu Wenbin,Wu Yaosen,Chen Jiaoxiang,Chu Junjie,Shen Panyang,Weng Sheji,Wang Xiangyang,Shen Lifeng,Fan Shunwu,Shen Shuying 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Low back pain, triggered by intervertebral disc degeneration (IVDD), is one of the most common causes of disability and financial expenditure worldwide. However, except for surgical interventions, effective medical treatment to prevent the progression of IVDD is lacking. This study aimed to investigate the effects of circKIF18A, a novel circRNA, on IVDD progression and to explore its underlying mechanism in IVDD. In this study, we found that oxidative stress was positively correlated with nucleus pulposus cell (NPC) senescence in IVDD and that circKIF18A was downregulated in IVDD and attenuated senescent phenotypes such as cell cycle arrest and extracellular matrix degradation in NPCs. Mechanistically, circKIF18A competitively suppressed ubiquitin-mediated proteasomal degradation of MCM7, and the protective effects of circKIF18A on NPCs were partially mediated by MCM7 under oxidative stress. Intradiscal injection of adenoviral circKIF18A ameliorated IVDD in a rat model. This study revealed that circKIF18A regulates NPC degeneration by stabilizing MCM7 and identified a novel signaling pathway, the circKIF18A-MCM7 axis, for anti-senescence molecular therapy in IVDD.
circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3
Huang Yizhen,Zhang Zhenlei,Wang Jianle,Shen Shuying,Yao Teng,Xu Yining,Chen Zizheng,Fang Bin,Ma Jianjun 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-
The abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene ( ATP1B3 ) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3 . The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.