Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Front Immunol. 2021 Feb 22;12:628654. doi: 10.3389/fimmu.2021.628654. eCollection 2021.
Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.
环状 RNA(circRNAs)的失调参与了多种人类疾病。成纤维样滑膜细胞(FLSs)形成关节的衬里,具有侵袭性表型的表观遗传印迹,并有助于类风湿关节炎(RA)中的关节破坏。在本研究中,我们鉴定了一种新型环状 RNA Circ_0088194,其在 RA 成纤维样滑膜细胞(RA-FLSs)中上调,并与 28 个关节的疾病活动评分相关。Circ_0088194 的过表达促进了 RA-FLS 的迁移和侵袭,而 Circ_0088194 的抑制则产生相反的效果。机制上,Circ_0088194 作为 miR-766-3p 的海绵,解除了 miR-766-3p 对其靶基因 (编码基质金属蛋白酶 2)的抑制作用,从而促进了迁移和侵袭。Circ_0088194 的表达水平与 RA-FLSs 中 miR-766-3p 的表达水平呈负相关。重要的是,miR-766-3p 的过表达部分阻断了 Circ_0088194 过表达诱导的迁移和侵袭。总之,这项研究鉴定了一种新型环状 RNA Circ_0088194,其通过 miR-766-3p/MMP2 轴促进 RA-FLS 的侵袭和迁移。Circ_0088194 可能代表了一种预防和治疗 RA 的新的治疗靶点。