{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:28:53Z","timestamp":1773926933577,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Curcumin has demonstrated antitumor efficacy, and its therapeutic and adjunct potential is increasingly supported by evidence. However, the anticancer mechanisms of curcumin in combination with chemotherapy remain complex and heterogeneous, warranting further investigation. Although 5\u2010fluorouracil (5\u2010FU)\u2010based chemotherapy remains a cornerstone of colorectal cancer (CRC) management, the emergence of chemoresistance significantly limits its clinical application. Therefore, the present work focused on elucidating the role of curcumin in modulating 5\u2010FU sensitivity and exploring the underlying molecular mechanism. Initially, we validated the antitumor effects of curcumin both in vivo and in vitro, and demonstrated its synergistic efficacy when combined with 5\u2010FU. We further identified circ\u2010NRIP1 as a target of curcumin and confirmed that curcumin enhances 5\u2010FU sensitivity in CRC cells by downregulating circ\u2010NRIP1 level. Mechanistic studies revealed that circ\u2010NRIP1 suppresses SMURF1 expression by competitively binding to miR\u2010195\u20105p, leading to AKT pathway activation, inhibition of apoptosis, and ultimately reduced 5\u2010FU sensitivity in CRC cells. Collectively, our findings verify that curcumin modulates 5\u2010FU sensitivity in CRC to through the circ\u2010NRIP1\/miR\u2010195\u20105p\/SMURF1\/AKT regulatory axis, providing a novel strategic approach for clinical CRC treatment.<\/jats:p>","DOI":"10.1002\/jbt.70775","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:59:41Z","timestamp":1773032381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Curcumin Modulates 5\u2010fluorouracil Sensitivity in Colorectal Cancer Cells Through the circ\u2010NRIP1\/miR\u2010195\u20105p\/SMURF1\/AKT Signaling Axis"],"prefix":"10.1002","volume":"40","author":[{"given":"You","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy Xi'an Eighth Hospital Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of 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