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LncRNA linc00152/NF-κB feedback loop promotes fibroblast-like synovial cells inflammation in rheumatoid arthritis via regulating miR-103a/TAK1 axis and YY1 expression
Immunity, Inflammation and Disease ( IF 2.493 ) Pub Date : 2021-06-01 , DOI: 10.1002/iid3.417
Jian Zhang 1 , Fei-Fei Gao 1 , Jie Xie 2
Affiliation  

Introduction: Overexpressed inflammatory cytokines are the main factors causing rheumatoid arthritis (RA) tissue damage and pathological deterioration, and lncRNAs has found to beinvolved in some autoinflammatory diseases. Methods: We designed this study to investigate the effect of lncRNA linc00152 on rheumatoid arthritis inflammation and explore its molecular mechanism.Result: We found that linc00152 was not only up-regulated in rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), but also stimulated by TNF-α/IL-1β in adose- and time-dependent manner in RAFLS and this expression depends on the NF-κB signaling pathway. Conversely, linc00152 promoted TNF-α/IL-1β expression in RAFLS induced by TNF-α/IL-1β. In addition, we found that linc00152 promoted TAK1 expression by targeting inhibition of miR-103a and activated TAK1-mediated NF-κB pathway. NF-kB indirectly promotes linc00152 expression by promoting the transcription activity of YY1, and YY1 directly promotes linc00152 expression by binding the promoter of linc00152. Conclusion: Our data suggested that the linc00152/NF-κB feedback loop promotes RAFLS inflammation via regulating miR-103a/TAK1 axis and YY1 expression. Thus, linc00152 acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.

中文翻译:

LncRNA linc00152/NF-κB反馈环通过调节miR-103a/TAK1轴和YY1表达促进类风湿性关节炎成纤维样滑膜细胞炎症

简介:过表达的炎症细胞因子是引起类风湿性关节炎(RA)组织损伤和病理恶化的主要因素,而lncRNA已被发现与一些自身炎症性疾病有关。方法:我们设计本研究旨在探讨lncRNA linc00152对类风湿性关节炎炎症的影响并探讨其分子机制。结果:我们发现 linc00152 不仅在类风湿性关节炎成纤维细胞样滑膜细胞 (RAFLS) 中上调,而且在 RAFLS 中以剂量和时间依赖性方式受到 TNF-α/IL-1β 的刺激,并且这种表达取决于NF-κB 信号通路。相反,linc00152 促进 TNF-α/IL-1β 诱导的 RAFLS 中 TNF-α/IL-1β 的表达。此外,我们发现linc00152通过靶向抑制miR-103a并激活TAK1介导的NF-κB通路来促进TAK1表达。NF-kB通过促进YY1的转录活性间接促进linc00152的表达,YY1通过结合linc00152的启动子直接促进linc00152的表达。结论:我们的数据表明 linc00152/NF-κB 反馈环路通过调节 miR-103a/TAK1 轴和 YY1 表达促进 RAFLS 炎症。因此,linc00152充当控制该调节回路的开关,并且可以作为RA治疗的诊断和治疗靶点。
更新日期:2021-08-07
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