{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:31:54Z","timestamp":1768800714127,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T00:00:00Z","timestamp":1695513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360190"],"award-info":[{"award-number":["82360190"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Oral submucous fibrosis (OSF) is associated with malignant disorders. DNA methyltransferase 3A (DNMT3A) is a DNA methylesterase reported to be upregulated in multiple organs and shown to inhibit fibrosis. However, the detailed effect of DNMT3A on OSF remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To mimic OSF in vitro, oral fibroblasts were exposed to arecoline and molecular biological experiments were performed to detect the function of DNMT3A in OSF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that von Hippel\u2013Lindau (VHL) was downregulated and highly methylated in OSF. Arecoline remarkably increased the viability, invasiveness, and migration of oral fibroblasts, but upregulation of VHL partially reversed these effects. DNMT3A induces DNA hypermethylation in the VHL promoter, and VHL markedly inhibits the level of tenascin\u2010C (TNC) by inducing the ubiquitination of TNC. TNC reversed the inhibitory effect of VHL upregulation on the differentiation of oral fibroblasts into myofibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DNMT3A induces OSF by promoting methylation of the VHL promoter. Hence, our study provides novel insights into the discovery of novel strategies that can be employed against OSF.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.14725","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T05:07:04Z","timestamp":1695618424000},"page":"2325-2336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["DNA methyltransferase 3A induces the occurrence of oral submucous fibrosis by promoting the methylation of the von Hippel\u2013Lindau"],"prefix":"10.1111","volume":"30","author":[{"given":"Huifang","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiyue","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The People's Hospital of Longhua  Shenzhen China"},{"name":"Research and Development Department Shenzhen Uni\u2010Medica Technology Co., Ltd  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8681-3691","authenticated-orcid":false,"given":"Wen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Hainan Medical University  Haikou China"},{"name":"School of Stomatology Hainan Medical University  Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030320"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00385.2009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62702-5.00010-X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122462"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94132-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009138"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000221"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S337014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110352"},{"issue":"3","key":"e_1_2_9_11_1","first-page":"307","article-title":"AML\u2010associated mutations in DNA methyltransferase DNMT3A","volume":"86","author":"Khrabrova D. 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