{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:16:18Z","timestamp":1788243378643,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0911600"],"award-info":[{"award-number":["2021YFA0911600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The activation of ferroptosis, a cell death mechanism driven by excessive ferrous ions (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ) and lipid peroxides, has emerged as a promising target for cancer treatment. However, in the case of quantitative regulation of target genes, it remains uncertain whether ferroptosis can be induced in bladder cancer (BCa) cells without affecting normal ones. We investigated this using an innovative CRISPR\u2010dCas9 system to upregulate and downregulate the ferroptosis\u2010related gene BECN1 and OTUB1, respectively. We identified two genes that can affect and promote ferroptosis\u2010related pathways, analysing their expression in bladder tissue through The Cancer Genome Atlas. Our unique CRISPR\u2010dCas9 technology, under the control of an hTERT promoter, selectively adjusted BECN1 and OTUB1 expression exclusively in cancer cells. RT\u2010qPCR and western blotting demonstrated significant alterations in the expression of GPX4 and SLC7A11, proteins strongly associated with ferroptosis, in BCa cells, while normal bladder cells remained unaffected. We developed a quantitative model based on synthetic biology principles to describe the regulatory relationships between the ferroptosis\u2010related genes BECN1 and OTUB1 and their downstream targets GPX4 and SLC7A11 in bladder cancer cells. The model establishes a direct proportional relationship between BECN1 upregulation and decreased GPX4 expression, and between OTUB1 downregulation and decreased SLC7A11 expression. In\u00a0vitro experiments revealed reduced viability, proliferation, migration, and invasion in UMUC\u20103 and T24 BCa cells. Importantly, Fer\u20101 and DFO rescued the viability loss, and C11\u2010BODIPY staining confirmed increased lipid ROS accumulation, supporting ferroptosis\u2010associated cell death following BECN1\/OTUB1 regulation. In\u00a0vivo xenograft experiments showed that BECN1 upregulation or OTUB1 downregulation suppressed tumour growth. Tumour\u2010tissue immunofluorescence further showed reduced GPX4 expression in BECN1\u2010upregulated tumours and reduced SLC7A11 expression in OTUB1\u2010downregulated tumours, supporting suppression of the GPX4\/SLC7A11 ferroptosis\u2010protective axis in\u00a0vivo. The quantitative equation derived from our data suggests that the induction of ferroptosis in bladder cancer cells can be effectively modulated by these two genes, and the experimental results also indicate our system can modulate these two genes to affect the function of BCa cells without affecting the normal cells, offering a promising new direction for the development of targeted therapy for bladder cancer.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71333","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:00:39Z","timestamp":1787742039000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative and Targeted Regulation of Ferroptosis in Bladder Cancer: Preclinical Study"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5643-8462","authenticated-orcid":false,"given":"Ying","family":"Dong","sequence":"first","affiliation":[{"name":"Shenzhen University Medical School, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital Shenzhen University  Shenzhen China"},{"name":"Shenzhen Institute of Translational Medicine, Urology of Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center Shenzhen University  Shenzhen China"},{"name":"Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9609-1848","authenticated-orcid":false,"given":"Chaojie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University First Hospital Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Yan","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Translational Medicine, Urology of Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center Shenzhen University  Shenzhen China"},{"name":"Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanzhu","family":"Mou","sequence":"additional","affiliation":[{"name":"Shenzhen Institute of Translational Medicine, Urology of Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center Shenzhen University  Shenzhen China"},{"name":"Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen 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