{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T11:43:11Z","timestamp":1770464591186,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873986"],"award-info":[{"award-number":["81873986"]}],"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","award":["82102533"],"award-info":[{"award-number":["82102533"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SFs) play a major role in cartilage and bone destruction through tumor\u2212like proliferation, migration, and invasion. Circular RNAs (circRNAs) have emerged as vital regulators for tumor progression. However, the regulatory role, clinical significance, and underlying mechanisms of circRNAs in RASF tumor\u2212like growth and metastasis remain largely unknown. Differentially expressed circRNAs in synovium samples from patients with RA and patients with joint trauma were identified via RNA sequencing. Subsequently, in vitro and in vivo experiments were performed to investigate the functional roles of circCDKN2B\u2212AS_006 in RASF proliferation, migration, and invasion. CircCDKN2B\u2212AS_006 was upregulated in synovium samples from patients with RA and promoted the tumor-like proliferation, migration, and invasion of RASFs. Mechanistically, circCDKN2B\u2212AS_006 was shown to regulate the expression of runt\u2212related transcription factor 1 (RUNX1) by sponging miR-1258, influencing the Wnt\/\u03b2\u2212catenin signaling pathway, and promoting the epithelial\u2212to\u2212mesenchymal transition (EMT) in RASFs. Moreover, in the collagen\u2212induced arthritis (CIA) mouse model, intra\u2212articular injection of lentivirus\u2212shcircCDKN2B\u2212AS_006 was capable of alleviating the severity of arthritis and inhibiting the aggressive behaviors of SFs. Furthermore, the correlation analysis results revealed that the circCDKN2B\u2212AS_006\/miR\u22121258\/RUNX1 axis in the synovium was correlated with the clinical indicators of RA patients. CircCDKN2B\u2212AS_006 promoted the proliferation, migration, and invasion of RASFs by modulating the miR\u22121258\/RUNX1 axis.<\/jats:p>","DOI":"10.3390\/ijms24065880","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T07:56:37Z","timestamp":1679298997000},"page":"5880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Circular RNA CircCDKN2B\u2212AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR\u22121258\/RUNX1 Axis"],"prefix":"10.3390","volume":"24","author":[{"given":"Yayun","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoyan","family":"Zai","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewen","family":"Qian","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Tao","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Peng","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feihu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230032, China"},{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China"},{"name":"The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.semarthrit.2006.08.006","article-title":"Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: A systematic 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