{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T13:03:36Z","timestamp":1779714216790,"version":"3.53.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    DNA methylation, is catalyzed by DNA methyltransferases (DNMTs), and its aberrant patterns are implicated in thyroid cancer pathogenesis. The study aimed to investigate the association of DNMTs with thyroid cancer and evaluated the effects of sustained demethylating therapy in a cell\u2010based study. DNMTs expressions in thyroid cancer were analyzed using GEO and TCGA datasets. Additionally, 16 paired and three unpaired papillary thyroid carcinoma (PTC) samples from Taipei Medical University (TMU), along with commercial tissue arrays, were analyzed. Furthermore, the effects of the covalent DNMT inhibitor, 5\u2010azacytidine (5\u2010Aza), and the DNMT1\u2010selective inhibitor, GSK\u20103484862, on cell viability were evaluated in PTC and follicular thyroid carcinoma (FTC) cell lines. DNMT1 and DNMT3A were upregulated in PTC, with DNMT1 expression correlated with the\n                    <jats:italic>BRAF<\/jats:italic>\n                    mutation and lymph node invasion in TCGA data, findings further confirmed in the TMU cohort and tissue arrays. Short\u2010term (24\u2009h) 5\u2010Aza treatment (1 and 5\u2009\u00b5M) induced substantial cell death regardless of the DNA methylation status, whereas short\u2010term GSK\u20103484862 (5\u2009\u00b5M) treatment showed minimal cytotoxicity. In contrast, sustained low\u2010dose GSK\u20103484862 treatment (approximately 1\u20133\u202fweeks at 2\u2009\u00b5M) effectively reduced global DNA methylation and decreased cell viability of TPC\u20101 and FTC\u2010236 cells through apoptosis, rather than by inhibiting proliferation. In conclusion, DNMT1 overexpression in PTC suggests its involvement in thyroid carcinogenesis. Sustained inhibition of DNMT1 effectively reduced global DNA methylation and promoted apoptosis, highlighting the potential of prolonged DNMT1\u2010targeted therapy. Further in vitro and in vivo studies are warranted to validate these results and elucidate the underlying mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70299","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:11:41Z","timestamp":1777403501000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustained DNA Hypomethylation Induced by a DNA Methyltransferase 1 Inhibitor Triggers Apoptosis in Thyroid Cancer Cells"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-6630","authenticated-orcid":false,"given":"Chao\u2010Wen","family":"Cheng","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine Taipei Medical University Taipei Taiwan,ROC"},{"name":"Traditional Herbal Medicine Research Center, Taipei Medical University Hospital Taipei Medical University Taipei Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Fang","family":"Fang","sequence":"additional","affiliation":[{"name":"Leader Clinic Taipei Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine Taipei Medical University Taipei Taiwan,ROC"},{"name":"Department of Medical Research, Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan, ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yea\u2010Mey","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine Taipei Medical University Taipei Taiwan,ROC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiunn\u2010Diann","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan, ROC"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine Taipei Medical University Taipei 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