{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:12:25Z","timestamp":1778177545515,"version":"3.51.4"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010230","name":"Qinghai University","doi-asserted-by":"publisher","award":["Qinghai Weijianwei [2023]133"],"award-info":[{"award-number":["Qinghai Weijianwei [2023]133"]}],"id":[{"id":"10.13039\/501100010230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>A close relationship exists between inflammation and cancer. Recent studies have highlighted inflammation as a significant contributor to the progression of bladder cancer. However, the role of alkyladenine DNA glycosylase homolog 2 (AlkBH2), an enzyme involved in DNA repair and a member of the AlkB family, in the context of bladder cancer inflammation remains largely unexplored. Our findings demonstrate that AlkBH2 promotes the proliferation, colony formation, migration, and invasion of bladder cancer cells. Mechanistically, AlkBH2 activates the nuclear factor-kappa B (NF-\u03baB) signaling pathway, which in turn drives the progression of bladder cancer. These results suggest that AlkBH2 plays a critical oncogenic role in bladder cancer by modulating inflammation through the activation of the NF-\u03baB pathway. These findings highlight the potential of AlkBH2 as a therapeutic target for bladder cancer treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0348059","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:29:09Z","timestamp":1778174949000},"page":"e0348059","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A new target: AlkBH2 promotes bladder cancer by upregulation of 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relation to NF-kB, cytokines, ceramide salvage sphingolipid pathway and PKC-zeta: hypothesis and review","volume":"7","author":"BM Altura","year":"2014","journal-title":"Int J Clin Exp Med"},{"issue":"5","key":"pone.0348059.ref025","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1177\/03009858221092017","article-title":"Review: NF-kB activation in canine cancer","volume":"59","author":"LJ Schlein","year":"2022","journal-title":"Vet Pathol"},{"key":"pone.0348059.ref026","doi-asserted-by":"crossref","first-page":"109129","DOI":"10.1016\/j.intimp.2022.109129","article-title":"Chicoric acid attenuates tumor necrosis factor-\u03b1-induced inflammation and apoptosis via the Nrf2\/HO-1, PI3K\/AKT and NF-\u03baB signaling pathways in C28\/I2 cells and ameliorates the progression of osteoarthritis in a rat model","volume":"111","author":"Y Qu","year":"2022","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"pone.0348059.ref027","first-page":"70","article-title":"MV1035 Overcomes Temozolomide Resistance in Patient-Derived Glioblastoma Stem Cell Lines","volume":"11","author":"A Malacrida","year":"2022","journal-title":"Biology (Basel)"},{"issue":"20","key":"pone.0348059.ref028","doi-asserted-by":"crossref","first-page":"12378","DOI":"10.1093\/nar\/gkae818","article-title":"3,N4-Etheno-5-methylcytosine blocks TET1-3 oxidation but is repaired by ALKBH2, 3 and FTO","volume":"52","author":"J Ma","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"14","key":"pone.0348059.ref029","doi-asserted-by":"crossref","first-page":"6620","DOI":"10.1093\/nar\/gks327","article-title":"The DNA dioxygenase ALKBH2 protects Arabidopsis thaliana against methylation damage","volume":"40","author":"TJ Meza","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"pone.0348059.ref030","unstructured":"Editor. Case of a Large and Several Smaller Encysted Tumors in the Right Ovarium, Being Discharged through an Opening in the Abdominal Parietes, Consequent on Suppurative Inflammation. Lond Med Phys J. 1822;47(280):463\u20136. 30494405"},{"issue":"1","key":"pone.0348059.ref031","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1186\/s13256-024-04835-2","article-title":"Coexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid: a case report","volume":"18","author":"AP Singh","year":"2024","journal-title":"J Med Case Rep"},{"issue":"6","key":"pone.0348059.ref032","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.3390\/cancers14061415","article-title":"Inflammation of the Pleural Cavity: A Review on Pathogenesis, Diagnosis and Implications in Tumor Pathophysiology","volume":"14","author":"G Karpathiou","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"4","key":"pone.0348059.ref033","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1142\/S0192415X23500416","article-title":"Ginsenosides are Promising Medicine for Tumor and Inflammation: A Review","volume":"51","author":"J Li","year":"2023","journal-title":"Am J Chin Med"},{"issue":"1","key":"pone.0348059.ref034","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1186\/s12885-025-14261-2","article-title":"INHBA+ macrophages and Pro-inflammatory CAFs are associated with distinctive immunosuppressive tumor microenvironment in submucous Fibrosis-Derived oral squamous cell carcinoma","volume":"25","author":"S Zhao","year":"2025","journal-title":"BMC Cancer"},{"issue":"15","key":"pone.0348059.ref035","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.2174\/1389557522666220307170126","article-title":"Medicinal Plants in Cancer Treatment: Contribution of Nuclear Factor- Kappa B (NF-kB) Inhibitors","volume":"22","author":"R Das","year":"2022","journal-title":"Mini Rev Med Chem"},{"key":"pone.0348059.ref036","doi-asserted-by":"crossref","first-page":"1513422","DOI":"10.3389\/fphar.2024.1513422","article-title":"An updated review summarizing the anticancer potential of flavonoids via targeting NF-kB pathway","volume":"15","author":"P Pandey","year":"2025","journal-title":"Front Pharmacol"},{"key":"pone.0348059.ref037","doi-asserted-by":"crossref","first-page":"111936","DOI":"10.1016\/j.cellsig.2025.111936","article-title":"ADSC exosomes improve high glucose induced fibroblast oxidative stress injury and accelerate DFU wound healing via regulating Keap1\/Nrf2 axis","volume":"134","author":"C Tian","year":"2025","journal-title":"Cell Signal"},{"key":"pone.0348059.ref038","doi-asserted-by":"crossref","first-page":"8273732","DOI":"10.1155\/2024\/8273732","article-title":"Moxibustion Regulates the BRG1\/Nrf2\/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer","volume":"2024","author":"X Wang","year":"2024","journal-title":"J Immunol Res"},{"key":"pone.0348059.ref039","doi-asserted-by":"crossref","first-page":"102576","DOI":"10.1016\/j.tice.2024.102576","article-title":"Attenuation of inflammation, oxidative stress and TGF-\u03b21\/Smad3 signaling and upregulation of Nrf2\/HO-1 signaling mediate the protective effect of diallyl disulfide against cadmium nephrotoxicity","volume":"91","author":"RS Alruhaimi","year":"2024","journal-title":"Tissue Cell"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0348059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:29:18Z","timestamp":1778174958000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0348059"}},"subtitle":[],"editor":[{"given":"Soumen","family":"Bera","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0348059","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]}}}