Abstract
Circular RNA_0004712 (circ_0004712) is reported to be up-regulated in rheumatoid arthritis (RA) patients. Nevertheless, its role and mechanism in RA pathology remain to be clarified. RNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, proliferation, apoptosis, migration, and inflammation were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-20-deoxyuridine assay, flow cytometry, scratch test, and enzyme-linked immunosorbent assay. The target correlation between microRNA-633 (miR-633) and circ_0004712 or TNF receptor associated factor 6 (TRAF6) was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0004712 was up-regulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0004712 silencing suppressed the viability, proliferation, migration and inflammatory response and facilitated the apoptosis of RA-FLSs. miR-633 was confirmed to be a direct target of circ_0004712, and miR-633 knockdown reversed circ_0004712 silencing-mediated protective effects on the dysfunction and inflammation of RA-FLSs. TRAF6 was a direct target of miR-633, and miR-633 overexpression suppressed the aggressive changes of RA-FLSs by down-regulating TRAF6. Circ_0004712 could up-regulate TRAF6 expression by sponging miR-633 in RA-FLSs. Circ_0004712 interference inactivated nuclear factor (NF)-κB signaling by targeting miR-633/TRAF6 axis. Circ_0004712 silencing inhibited the aggressive changes of RA-FLSs by targeting miR-633/TRAF6 axis and NF-κB signaling, which provided new targets for RA therapy.
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Abbreviations
- RA:
-
Rheumatoid arthritis
- ELISA:
-
Enzyme-linked immunosorbent assay
- RA-FLSs:
-
RA fibroblast-like synoviocytes
- PDE7B:
-
Phosphodiesterase 7B
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SZ: conceived and designed the study, and drafted the first draft of the manuscript. All experiments were completed by all authors. ZS, GC, XD, WZ, DJ, YL: analyzed and collated the results. All authors reviewed and critiqued the manuscript, and agreed to the final submission of the manuscript. All authors read and approved the final manuscript.
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Zhang, S., Shen, Z., Chao, G. et al. Circ_0004712 Silencing Suppresses the Aggressive Changes of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting miR-633/TRAF6 Axis. Biochem Genet 61, 521–537 (2023). https://doi.org/10.1007/s10528-022-10265-w
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DOI: https://doi.org/10.1007/s10528-022-10265-w