{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:23Z","timestamp":1789016843310,"version":"build-2803163510"},"reference-count":21,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303623"],"award-info":[{"award-number":["82303623"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82303623"],"award-info":[{"award-number":["82303623"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>This study examined how 1-hydroxypyrene (1-OHP) affects bladder cancer (BCa) progression and tumor-associated immunosuppression. Public transcriptomic data and target-prediction databases were used to screen for targets related to 1-OHP and BCa. Machine learning was then used to narrow down the candidate genes. Molecular docking and single-cell RNA sequencing were also used to examine the selected targets and related pathways. The role of the main target was tested in vitro. CCK-8, colony formation, EdU, and Transwell assays were used to assess cell growth, migration, and invasion. Protein expression was examined by Western blotting. A tumor cell\u2013CD8+ T-cell co-culture system was used to evaluate changes in CD8+ T-cell function. We identified 29 targets shared by 1-OHP and BCa. Machine learning further narrowed these targets to six genes, and macrophage migration inhibitory factor (MIF) was chosen for experimental validation. Treatment with 1-OHP increased BCa cell viability, proliferation, migration, and invasion. Silencing MIF partly reduced these effects. 1-OHP also increased MIF and CD74\/CD44 expression and enhanced PI3K\/AKT\/mTOR signaling. These changes were reduced after MIF silencing. In the co-culture system, 1-OHP-treated BCa cells reduced CD8+ T-cell proliferation and function. Ki67, GZMB, and IFNG levels were decreased. MIF knockdown partly reversed these changes. Collectively, our findings show that 1-OHP promotes bladder cancer progression and tumor-associated immunosuppression, at least in part, through a MIF-dependent mechanism. By linking environmental exposure to activation of the CD74\/CD44\u2013PI3K\/AKT\/mTOR axis and impaired CD8+ T-cell function, our study provides new insight into the molecular basis of environmentally associated bladder carcinogenesis.<\/jats:p>","DOI":"10.3390\/ijms27177778","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["1-Hydroxypyrene Promotes Bladder Cancer Progression and Tumor-Associated Immunosuppression via MIF"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-3290","authenticated-orcid":false,"given":"Yiting","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Minimally Invasive Treatment of Urology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Minimally Invasive Treatment of Urology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Minimally Invasive Treatment of Urology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Minimally Invasive Treatment of Urology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5459-5204","authenticated-orcid":false,"given":"Lilong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Provincial Clinical Research Center for Minimally Invasive Treatment of Urology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.eururo.2023.03.029","article-title":"Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors","volume":"84","author":"Jubber","year":"2023","journal-title":"Eur. 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