Circ_0088200 可作为 miR-127-5p 的海绵,促进类风湿性关节炎成纤维细胞样滑膜细胞的迁移和侵袭。

Rheumatology and immunology research Pub Date : 2025-04-02 eCollection Date: 2025-03-01 DOI:10.1515/rir-2025-0002
Yujie Cai, Rong Qiu, Qin Huang, Weinan Lai, Yipeng Han, Xiaoxi Lu, Jiayu Qin, Qingqing Ouyang, Min Yang
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引用次数: 0

摘要

背景:环状rna (circRNAs)在多种疾病的发生发展中起着至关重要的作用。然而,很少有研究调查环状rna在类风湿关节炎(RA)中的作用。在此,我们旨在鉴定参与RA成纤维细胞样滑膜细胞(RA- fls)迁移和侵袭的新型环状rna。方法:从RA患者的滑膜中分离RA- fls。通过CircRNA微阵列分析筛选CircRNA谱。采用实时定量逆转录聚合酶链反应(qRT-PCR)检测Circ_0088200和miR-127-5p的表达水平。western blotting检测基质金属蛋白酶1 (MMP1)蛋白表达水平。采用伤口愈合和Transwell实验分析RA-FLS的迁移和侵袭。采用RNA免疫沉淀(RIP)和双荧光素酶报告基因检测来验证Circ_0088200和miR-127-5p之间的相互作用。建立胶原诱导关节炎(CIA)小鼠模型,评估Circ_0088200在体内关节炎发展中的作用。结果:与骨关节炎成纤维细胞样滑膜细胞(OAFLS)相比,Circ_0088200在RA-FLS中高表达,并与28个关节的疾病活动度评分呈正相关。抑制Circ_0088200抑制了RA-FLS的迁移和侵袭。相反,过表达Circ_0088200可显著促进RA-FLS的迁移和侵袭。在机制上,Circ_0088200作为miR-127-5p的海绵,解除其对MMP1的抑制作用,从而促进RA-FLS的迁移和侵袭。重要的是,关节内注射表达Circ_0088200的腺相关病毒可显著增加CIA小鼠关节炎的严重程度。结论:Circ_0088200通过海绵化miR-127-5p促进RA-FLS的迁移和侵袭。因此Circ_0088200是RA的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circ_0088200 acts as a sponge for miR-127-5p to promote the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes.

Background: Circular RNAs (circRNAs) play a crucial role in the development of various diseases. However, few studies have investigated the role of circRNAs in rheumatoid arthritis (RA). Herein, we aimed to identified the novel circRNAs involved in the migration and invasion of RA fibroblast-like synoviocytes (RA-FLS).

Methods: The RA-FLS were isolated from the synovial membrane of patients with RA. The CircRNA profile was screened by CircRNA microarray analysis. Circ_0088200 and miR-127-5p expression levels were detected using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The protein level of matrix metalloproteinase 1 (MMP1) was evaluated by western blotting. Wound healing and Transwell assays were performed to analyze the migration and invasion of RA-FLS. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to validate the interaction between Circ_0088200 and miR-127-5p. Collagen-induced arthritis (CIA) mouse models were established to evaluate the role of Circ_0088200 in the development of arthritis in vivo.

Results: Circ_0088200 was highly expressed in RA-FLS compared with osteoarthritis fibroblast-like synoviocytes (OAFLS) and correlated positively with the disease activity score in 28 joints. Inhibition of Circ_0088200 suppressed the migration and invasion of RA-FLS. Conversely, overexpression of Circ_0088200 significant promoted the migration and invasion of RA-FLS. Mechanistically, Circ_0088200 functions as a sponge for miR-127-5p and relieve its repressive effect on MMP1, thereby promoting the migration and invasion of RA-FLS. Importantly, intra-articular injection of Adenoassociated virus expressing Circ_0088200 significantly increased the severity of arthritis in mice with CIA.

Conclusion: Circ_0088200 promotes the migration and invasion of RA-FLS by sponging miR-127-5p. Thus Circ_0088200 is a potential therapeutic target for RA.

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