DataSheet_1_Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.doc

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, MMP2 (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 via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.

循环RNA（circRNAs）的失调参与多种人类疾病的发生。成纤维细胞样滑膜细胞（FLSs），作为关节衬里的重要组成部分，在类风湿性关节炎（RA）中通过表观遗传学机制获得侵袭性表型，从而加剧关节的破坏。在本研究中，我们鉴定了一种新型的circRNA，即Circ_0088194，其在RA成纤维细胞样滑膜细胞（RA-FLSs）中表达上调，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-FLSs的迁移和侵袭，而其抑制则产生相反的效果。从机制上讲，Circ_0088194作为miR-766-3p的竞争性结合蛋白，解除其对靶基因MMP2（编码基质金属蛋白酶2）的抑制，从而促进迁移和侵袭。在RA-FLSs中，Circ_0088194的表达水平与miR-766-3p的表达水平呈负相关。值得注意的是，miR-766-3p的过表达部分阻断了Circ_0088194过表达所诱导的迁移和侵袭。综上所述，本研究鉴定了一种新型的circRNA Circ_0088194，该RNA通过miR-766-3p/MMP2轴促进RA-FLSs的侵袭和迁移。Circ_0088194可能成为预防和治疗RA的一种新的治疗靶点。