Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis

Abstract

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.

Expression Profile and Potential Function of Circular RNAs in Peripheral Blood Mononuclear Cells in Male Patients With Primary Gout

“…Therefore, the multi-functionality of circRNAs makes them ideal for researching and predicting disease. In recent years, increasing numbers of studies have shown that the abnormal expression of circRNAs is closely related to the development of a variety of rheumatisms, such as systemic lupus erythematosus ( Wang X. et al, 2021 ), rheumatoid arthritis ( Cai et al, 2021 ), and osteoarthritis ( Liu et al, 2021 ), etc., However, the role of circRNAs in gout is not well understood. In this study, genome-wide microarrays were used to analyze the circRNA expression profile in the PBMCs of gout patients.…”

Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

“…Cai et al identified that circ_0088194 was up-regulated in RA FLS; it could act as miR-766-3p sponge and promote the expression of downstream target gene MMP2, thereby facilitating the fibroblast−like synoviocytes' invasion and migration. It may be a novel and promising target for RA (167). Qu et al suggested that circ-AFF2 was up-regulated in synovial tissues and FLS of RA; circ-AFF2 could bind to the miRNA miR-650; it enhances the expression level of downstream target 2',3'-cyclic nucleotide phosphodiesterase (CNP) and promotes fibroblast−like synoviocyte proliferation, inflammatory response, migration, and invasion (168).…”

[Retracted] The Function of circRNA‐0047604 in Regulating the Tumor Suppressor Gene DACH1 in Breast Cancer

“…It is a single-stranded covalently closed circular transcripts which make it more stable and harder to degrade in cells [9]. Recently, circRNAs have been confirmed as diagnostic biomarkers of many diseases like cardiovascular diseases, rheumatoid arthritis, kidney disease, and cancer [10][11][12][13]. Nowadays, the underlying mechanism of circRNA function significantly lies in the miRNA or protein sponges, enhancer of protein function, protein scaffolding, protein recruitment, and templates for peptides translation [9].…”