{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:26:09Z","timestamp":1787574369449,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, ROC","award":["MOST 110-2314-B-303-024-MY2"],"award-info":[{"award-number":["MOST 110-2314-B-303-024-MY2"]}]},{"name":"Buddhist DaLin Tzu-Chi Hospital","award":["DTCRD112(2)-E-02-01"],"award-info":[{"award-number":["DTCRD112(2)-E-02-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ankylosing spondylitis (AS) is a chronic inflammatory disease strongly associated with human leukocyte antigen B27 (HLA-B27). However, the incomplete penetrance of HLA-B27 suggests that additional molecular mechanisms contribute to AS pathogenesis. Circular RNAs (circRNAs) have emerged as important regulators of immune responses, but their roles in AS pathogenesis remain incompletely understood. In this study, circRNA expression profiles were examined by high-throughput RNA sequencing and selected circRNAs were validated by quantitative RT-PCR in T cells from AS patients and healthy controls. Among the validated circRNAs, circRNPS1 was significantly up-regulated in T cells from AS patients. Overexpression of circRNPS1 in activated Jurkat cells increased IL-2, IL-17A, and interferon-\u03b3 expression and enhanced JAK2\/STAT1 and MEK1\/2-ERK signaling. RNA pull-down followed by proteomic analysis identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) that binds to the back-splicing junction region of circRNPS1. CircRNPS1 increased the stability of hnRNPK and VAV1, whereas hnRNPK knockdown attenuated circRNPS1-mediated MEK1\/2-ERK activation and inflammatory cytokine expression. Furthermore, an antisense RNA fragment targeting the back-splicing junction region of circRNPS1 suppressed IL-2, IL-17A, and interferon-\u03b3 expression in activated circRNPS1-overexpressing Jurkat cells and T cells from AS patients. Disrupting the interaction between circRNPS1 and hnRNPK therefore warrants further investigation as a potential therapeutic strategy for AS.<\/jats:p>","DOI":"10.3390\/ijms27177550","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Increased Circular RNA, circRNPS1, in T Cells of Ankylosing Spondylitis Patients Enhances the MEK\/ERK Signaling and Inflammation Mediated by T Cell Activation via Stabilization of hnRNPK and VAV1"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3728-6083","authenticated-orcid":false,"given":"Hui-Chun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Sheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Yung","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2015-8614","authenticated-orcid":false,"given":"Pin-Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-0351","authenticated-orcid":false,"given":"Ming-Chi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien-Bin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, National Chung Cheng University, Chiayi 62102, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.0105-2896.2009.00865.x","article-title":"From HLA-B27 to spondyloarthritis: A journey through the ER","volume":"233","author":"Colbert","year":"2010","journal-title":"Immunol. 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