DataSheet_2_Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.zip

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 (circRNA) 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)，构成关节的衬里，通过表观遗传学方式被赋予侵袭性表型，并在类风湿关节炎 (RA) 中促进关节的破坏。在本研究中，我们鉴定了一种新的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。机制上，Circ_0088194充当miR-766-3p海绵，从而缓解miR-766-3p对其靶标MMP2（编码基质金属蛋白酶2）的抑制效应，进而促进迁移和侵袭。在RA-FLSs中，Circ_0088194的表达水平与miR-766-3p的表达水平呈负相关。重要的是，miR-766-3p的过表达部分阻断了由Circ_0088194过表达诱导的迁移和侵袭。总之，本研究鉴定了一种新的circRNA Circ_0088194，通过miR-766-3p/MMP2轴促进RA-FLSs的侵袭和迁移。Circ_0088194可能代表一种新的治疗靶点，以预防和治疗RA。