{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:05:32Z","timestamp":1790139932211,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Circular RNAs (circRNAs) represent key regulators in cancer pathogenesis; however, their involvement in alternative splicing (AS) remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Expression of circFut8 was detected in bladder cancer (\n                      <jats:sc>BC<\/jats:sc>\n                      ) tissues\/cell lines; RNA pull\u2010down, cross\u2010linking immunoprecipitation (CLIP) assays verified circFut8's interaction with splicing factor SRSF9. CircFut8 overexpression was performed to assess its effects on\n                      <jats:sc>BC<\/jats:sc>\n                      cell proliferation in\u00a0vitro (CCK\u20108, colony formation) and tumor growth in\u00a0vivo (xenograft models), and its modulation of FUT8 pre\u2010mRNA splicing was analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here, we identify circFut8\u2014a conserved exonic circRNA originating from FUT8 gene exon 3\u2014as a\n                      <jats:sc>BC<\/jats:sc>\n                      tumor suppressor, which is significantly downregulated in\n                      <jats:sc>BC<\/jats:sc>\n                      tissues and cell lines, correlating with advanced tumor grade and invasion. Mechanistically, circFut8 competitively binds the splicing factor SRSF9, thereby modulating the inclusion\/exclusion of exon 3 in FUT8 pre\u2010mRNA and promoting the production of the FUT8\u20104 splice variant. Functional assays confirm that circFut8 overexpression inhibits\n                      <jats:sc>BC<\/jats:sc>\n                      proliferation in\u00a0vitro and suppresses tumor growth in\u00a0vivo, while RNA pull\u2010down and cross\u2010linking immunoprecipitation (CLIP) assays confirm its direct interaction with SRSF9.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings unveil a novel circRNA\u2010mediated regulatory axis wherein circFut8 fine\u2010tunes pre\u2010mRNA splicing through competition with SRSF9, suggesting its potential as a candidate for further therapeutic exploration.<\/jats:p>\n                  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