{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:55Z","timestamp":1785437995203,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>N7\u2010methylguanosine (m7G) represents a critical posttranscriptional modification linked to oncogenesis, but its involvement in prostate cancer (PCa) remains unclear. This study focuses on WD repeat domain 4 (WDR4) and methyltransferase like 1 (METTL1) to explore their function and therapeutic potential in PCa. Using qRT\u2010PCR, Western blot, m7G RNA immunoprecipitation (MeRIP), and functional assays (CCK\u20108, Transwell, TUNEL), we investigated how METTL1\/WDR4 regulate m7G modification, the PI3K\/AKT\/mTOR cascade, and target genes (MYC and VEGF), as well as their impact on DU145 cell growth, motility, invasion, and apoptosis. Both METTL1 and WDR4 were highly expressed in PCa samples and DU145 cells, correlated with elevated m7G tRNA modification levels. Their knockdown markedly inhibited DU145 cell growth, motility, and invasion, and facilitated apoptosis. These effects were associated with reduced m7G modification, suppression of the PI3K\/AKT\/mTOR pathway, and downregulation of MYC and VEGF expression, showing synergistic inhibitory effects. This study reveals that METTL1 and WDR4 are overexpressed in PCa and that, in DU145 cells, their knockdown was associated with suppressed m7G modification and attenuated oncogenic phenotypes. These model\u2010specific findings suggest that METTL1\/WDR4 may represent potential therapeutic targets in prostate cancer.<\/jats:p>","DOI":"10.1002\/jbt.70546","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:04:47Z","timestamp":1760598287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Insights Into METTL1\/WDR4\u2010Mediated m7G Modification in Prostate Cancer Progression and Its Potential as a Therapeutic Target"],"prefix":"10.1002","volume":"39","author":[{"given":"Wangdong","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Urology Longgang District Central Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanming","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathology Longgang District Central Hospital of Shenzhen Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Urology Longgang District Central Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology Longgang District Central Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology Longgang District Central Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuantang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Urology Longgang District Central Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1856-3951","authenticated-orcid":false,"given":"Zuomin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Longgang District Central Hospital of Shenzhen Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13593"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2020.08.007"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202302368"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-019-0172-z"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2024.8854"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000519861"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-024-01264-w"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111288"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.08.005"},{"issue":"5","key":"e_1_2_13_13_1","first-page":"1640","article-title":"N7\u2010methylguanosine Modification: From Regulatory Roles to Therapeutic Implications in Cancer","volume":"13","author":"Cai M.","year":"2023","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-024-08736-8"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0779-x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12273"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023017"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2023.100481"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.642080"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118731"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124507"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12771"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.05.001"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.82920"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102154"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103756"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1380746"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-022-02250-9"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02695-6"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02089-6"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1260195"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2016.00012"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0168-5"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70546","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70546","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:27:22Z","timestamp":1785436042000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jbt.70546"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70546","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]},"assertion":[{"value":"2025-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70546"}}