{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:58:33Z","timestamp":1787914713266,"version":"build-2784847793"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the effects of circ\u2010CBLB and ETS\u20101 on the proliferation, apoptosis, and inflammatory cytokine expression in the fibroblast\u2010like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood was collected from 15 pairs of healthy controls (HCs) and patients with RA to isolate peripheral blood mononuclear cells (PBMCs). mRNA expression of circ\u2010CBLB and ETS\u20101 was determined using qRT\u2010PCR. Levels of the inflammatory markers (ESR, CRP, CCP, and RF) were determined, and the 28\u2010joint Disease Activity Score (DAS28) was calculated. For in\u00a0vitro experiments, human FLS and RA\u2010FLS were cultured, and constructs (pcDNA3.1\/siRNA\u2010circ\u2010CBLB, pcDNA3.1\/siRNA\u2010ETS\u20101) were transfected into RA\u2010FLS. Cotransfection of pcDNA3.1\u2010circ\u2010CBLB and siRNA\u2010ETS\u20101 was undertaken to explore their combined effects. Levels of the key inflammatory cytokines (interleukin [IL]\u20104, IL\u201023, IL\u201013, and tumor necrosis factor [TNF]\u2010\u03b1) were evaluated using qRT\u2010PCR and enzyme\u2010linked immunosorbent assays. Functional assays (CCK\u20108) were used to assess cell viability, apoptosis (flow cytometry), and migration. Western blotting was used to determine protein expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vivo analysis showed significant downregulation of circ\u2010CBLB and ETS\u20101 in PBMCs from patients with RA compared with the HCs, as confirmed using qRT\u2010PCR. Correlation analysis indicated a positive association among circ\u2010CBLB, ETS\u20101, and IL\u20104, while circ\u2010CBLB and ETS\u20101 were negatively correlated with inflammatory markers (ESR, CRP, RF, CCP, DAS28, IL\u201023, and TNF\u2010\u03b1). Receiver operating characteristic curve analysis suggested circ\u2010CBLB and ETS\u20101 as potential biomarkers for high disease activity in RA. In\u00a0vitro, circ\u2010CBLB overexpression increased IL\u20104 levels while decreasing IL\u201023, IL\u201013, and TNF\u2010\u03b1 levels. Additionally, circ\u2010CBLB inhibited the apoptosis of RA\u2010FLS, prolonged the cell cycle, and reduced cell migration. ETS\u20101 negatively regulated circ\u2010CBLB, indicating a feedback loop.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>circ\u2010CBLB and ETS\u20101 are downregulated in RA and correlate with inflammation and disease activity. They regulate each other bidirectionally. circ\u2010CBLB reduces RA\u2010FLS viability, promotes apoptosis, and inhibits migration by modulating cytokines. ETS\u20101 has similar effects, and interfering with its expression reverses the impact of circ\u2010CBLB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.70167","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T11:05:07Z","timestamp":1742209507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Unraveling the Dual Role of circ\u2010<scp>CBLB<\/scp> and <scp>ETS<\/scp>\u20101 in Rheumatoid Arthritis: Biomarkers and Therapeutic Targets"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-2805","authenticated-orcid":false,"given":"Shu","family":"Li","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HaoXiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoJun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine  Hefei 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