{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:53:11Z","timestamp":1792079591653,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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 Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    NUPR1 is a pro\u2010tumorigenic factor in bladder cancer (BLCA), but the mechanisms governing its protein stability remain poorly defined. Here, we identified ARIH2 as an E3 ubiquitin ligase that interacts with NUPR1 in BLCA cells through immunoprecipitation\u2010mass spectrometry (IP\u2010MS), co\u2010immunoprecipitation (Co\u2010IP), and immunofluorescence analyses. ARIH2 overexpression reduced NUPR1 abundance and inhibited BLCA cell proliferation and migration while enhancing apoptosis, whereas ARIH2 knockdown increased NUPR1 expression and promoted malignant phenotypes. Mechanistically, ARIH2 depletion prolonged NUPR1 protein stability and reduced its ubiquitination, indicating that ARIH2 negatively regulates NUPR1 through ubiquitin\u2010mediated degradation. Moreover, NUPR1 overexpression suppressed ferroptosis, as reflected by increased GPX4 and SLC7A11, decreased ACSL4, reduced lipid peroxidation, and diminished Fe\n                    <jats:sup>2+<\/jats:sup>\n                    accumulation, while NUPR1 knockdown exerted the opposite effects. ARIH2 knockdown mimicked the ferroptosis\u2010resistant phenotype induced by NUPR1 upregulation, supporting that ARIH2 modulates ferroptosis through NUPR1. Bioinformatic and experimental analyses further showed that NUPR1 was associated with immunosuppressive infiltration and promoted M2 macrophage polarization. Together, our findings uncover an ARIH2\u2013NUPR1 regulatory axis that drives BLCA progression by suppressing ferroptosis and favouring an immunosuppressive microenvironment, highlighting this pathway as a potential therapeutic target in BLCA.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71147","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:56:42Z","timestamp":1776484602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>ARIH2<\/scp>\n                    Ubiquitination Regulates\n                    <scp>NUPR1<\/scp>\n                    to Inhibit Ferroptosis in Bladder Cancer"],"prefix":"10.1111","volume":"30","author":[{"given":"Hannuo","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Urology The Second People's Hospital of Changzhou, Changzhou Medical Center  Changzhou 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Medical Center  Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6260-2369","authenticated-orcid":false,"given":"Zebin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology The Second People's Hospital of Changzhou, Changzhou Medical Center  Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Urology The Second People's Hospital of Changzhou, Changzhou Medical Center  Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The Second People's Hospital of Changzhou, Changzhou Medical Center  Changzhou 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