The circ_0003692-miR-1197-TLR4 axis: A key regulator in rheumatoid arthritis proliferation and inflammation

Rheumatoid arthritis (RA) is a joint disease characterized by abnormal development of fibroblast-like synoviocytes (FLSs). Circular RNAs (circRNAs) possess momentous regulatory functions in human disease progression. This research was conducted to investigate regulatory mechanism of circ_0003692 in RA. In this research, circ_0003692 and Toll-like receptor 4 (TLR4) expressions were elevated in RA tissues and RA-fibroblast-like synoviocytes (RA-FLSs) (P < 0.05), but microRNA-1197 (miR-1197) level was decreased (P < 0.01). Functionally, circ_0003692 knockdown restrained RA-FLSs proliferation, inflammation, migration and invasion (P < 0.01). Mechanistically, miR-1197 was identified as a target for circ_0003692 and miR-1197 targeted TLR4. The expressions of circ_0003692 and TLR4 were positively correlated in RA, while miR-1197 and TLR4 expressions were negatively correlated in RA (P < 0.001). Rescue assay further authenticated that interference with circ_0003692 reduced RA-FLSs proliferation and inflammation through miR-1197/TLR4/nuclear factor-transcription factor B (NF-κB) (P < 0.05). In vivo research also vindicated that circ_0003692 knockdown alleviated CIA mice by reducing synovial tissue proliferation and inflammatory cell infiltration, relieving cartilage injury and reducing osteoclast formation in CIA mice (P < 0.05). In summary, interference with circ_0003692 reduced RA-FLSs proliferation and inflammation via miR-1197/TLR4/NF-κB.