LncRNA XIST promotes adjuvant-induced arthritis by increasing the expression of YY1 via miR-34a-5p.

IF 1.1 4区 医学 Q4 Medicine
Yazhi Wei, Liping Dai, Yanqun Deng, Zhizhong Ye
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Abstract

Objectives: This study aims to explore the mechanism by which long non-coding ribonucleic acids (lncRNA) X-inactive specific transcript (XIST) affects the progression of adjuvant-induced arthritis (AIA).

Materials and methods: Freund's complete adjuvant was used to induce arthritis in rats. The polyarthritis, spleen and thymus indexes were calculated to evaluate AIA. Hematoxylin-eosin (H&E) staining was used to reveal the pathological changes in the synovium of AIA rats. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-8 in the synovial fluid of AIA rats. The cell continuing kit (CCK)-8, flow cytometry, and Transwell assays were used to assess the proliferation, apoptosis, migration and invasion of transfected fibroblast-like synoviocytes (FLS) isolated from AIA rats (AIA-FLS). Dual-luciferase reporter assay was performed to verify the binding sites between XIST and miR-34b-5p or between YY1 mRNA and miR-34b-5p.

Results: The XIST and YY1 were highly expressed, and miR-34a-5p was lowly expressed in the synovium of AIA rats and in AIA-FLS. Silencing of XIST impaired the function of AIA-FLS in vitro and inhibited the progression of AIA in vivo. The XIST promoted the expression of YY1 by competitively binding to miR-34a-5p. Inhibition of miR-34a-5p strengthened the function of AIA-FLS by upregulating XIST and YY1.

Conclusion: The XIST controls the function of AIA-FLS and may promote the progression of rheumatoid arthritis via the miR-34a-5p/YY1 axis.

Abstract Image

Abstract Image

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LncRNA XIST通过miR-34a-5p增加YY1的表达来促进佐剂诱导的关节炎。
目的:本研究旨在探讨长链非编码核糖核酸(lncRNA) x无活性特异性转录物(XIST)影响佐剂性关节炎(AIA)进展的机制。材料与方法:采用弗氏完全佐剂诱导大鼠关节炎。计算多关节炎、脾脏和胸腺指数来评估AIA。采用苏木精-伊红(H&E)染色观察AIA大鼠滑膜的病理变化。采用酶联免疫吸附法(ELISA)检测AIA大鼠滑膜液中肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-6、IL-8的表达。采用细胞连续检测试剂盒(CCK)-8、流式细胞术和Transwell检测AIA大鼠(AIA-FLS)分离的纤维母细胞样滑膜细胞(FLS)的增殖、凋亡、迁移和侵袭。采用双荧光素酶报告基因试验验证XIST与miR-34b-5p之间或YY1 mRNA与miR-34b-5p之间的结合位点。结果:AIA大鼠滑膜及AIA- fls组织中XIST、YY1高表达,miR-34a-5p低表达。在体外,沉默XIST可损伤AIA- fls的功能,抑制AIA在体内的进展。XIST通过竞争性结合miR-34a-5p促进YY1的表达。抑制miR-34a-5p可通过上调XIST和YY1增强AIA-FLS的功能。结论:XIST通过miR-34a-5p/YY1轴调控ia - fls功能,促进类风湿关节炎的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archives of rheumatology
Archives of rheumatology Medicine-Rheumatology
CiteScore
2.00
自引率
9.10%
发文量
15
期刊介绍: The Archives of Rheumatology is an official journal of the Turkish League Against Rheumatism (TLAR) and is published quarterly in March, June, September, and December. It publishes original work on all aspects of rheumatology and disorders of the musculoskeletal system. The priority of the Archives of Rheumatology is to publish high-quality original research articles, especially in inflammatory rheumatic disorders. In addition to research articles, brief reports, reviews, editorials, letters to the editor can also be published. It is an independent peer-reviewed international journal printed in English. Manuscripts are refereed by a "double-blind peer-reviewed" process for both referees and authors. Editorial Board of the Archives of Rheumatology works under the principles of The World Association of Medical Editors (WAME), the International Council of Medical Journal Editors (ICMJE), and Committee on Publication Ethics (COPE).
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