{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:08:07Z","timestamp":1789524487410,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2024AAC03697"],"award-info":[{"award-number":["2024AAC03697"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2019AAC03200"],"award-info":[{"award-number":["2019AAC03200"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Exosomes, the cargo of circRNA, are crucial in cancer cell\u2013tumor microenvironment communication. circSMARCC1 exerts a pro\u2010tumor effect. However, this role has not been previously reported in gastric cancer (STAD). This study explores the role of STAD cell\u2010derived exosomal circSMARCC1 in promoting macrophage M2 polarization. In this study, exosomes from the peripheral blood of STAD patients and AGS cells were extracted and identified. THP\u20101 cells were differentiated into macrophages with phorbol 12\u2010myristate 13\u2010acetate (PMA) and polarized to the M2 phenotype by IL\u20104 and IL\u201013. circSMARCC1 expression was analyzed in STAD tissues, cell lines, and patient\u2010derived exosomes. The biological function of circSMARCC1 in STAD cells was evaluated by CCK\u20108, EdU, and Transwell assays. The role of circSMARCC1 and U2 small nuclear RNA auxiliary factor 2 (U2AF2) in regulating macrophage M2 polarization was verified by bioinformatics methods, qRT\u2010PCR, Western blot, ELISA, and a nude mouse tumor\u2010bearing model. Our findings demonstrated that circSMARCC1 was upregulated in STAD and associated with macrophage immune infiltration. circSMARCC1 knockdown suppressed the malignant phenotypes of STAD cells and M2 macrophage polarization, whereas its overexpression led to the contrary result. Animal experiments further confirmed circSMARCC1 regulated tumor growth and macrophage M2 polarization. Importantly, exosomal circSMARCC1 in STAD patients was increased. Knockdown of circSMARCC1 in AGS cells reduced its level in secreted exosomes and inhibited M2 polarization, whereas overexpression produced the opposite effect. Mechanistically, circSMARCC1 upregulated U2AF2 expression through exosomes to promote macrophage M2 polarization. Collectively, STAD cell\u2010derived exosomes induced macrophage M2 polarization to promote STAD progression through circSMARCC1.<\/jats:p>","DOI":"10.1002\/iub.70062","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T09:47:24Z","timestamp":1760608044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gastric Cancer Cell\u2010Derived Exosomes Induce Macrophage\n                    <scp>M2<\/scp>\n                    Polarization by Delivering\n                    <scp>circSMARCC1<\/scp>\n                    to Promote Gastric Cancer Progression"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6712-2279","authenticated-orcid":false,"given":"Cao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery General Hospital of Ningxia Medical University  Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Functional Examination, Cardiac Center General Hospital of Ningxia Medical University  Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Guan","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Ningxia Medical University  Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyi","family":"Fang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Ningxia Medical University  Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"E359","article-title":"Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in 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