{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:29:18Z","timestamp":1791916158221,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671711"],"award-info":[{"award-number":["81671711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Clinical efficacy of differentiation therapy with mitogen\u2010activated protein kinase inhibitors (MAPKi) for lethal radioiodine\u2010refractory papillary thyroid cancer (RR\u2010PTC) urgently needs to be improved and the aberrant trimethylation of histone H3 lysine 27 (H3K27) plays a vital role in\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600E<\/jats:sup>\n                    \u2010MAPK\u2010induced cancer dedifferentiation and drug resistance. Therefore, dual inhibition of MAPK and histone methyltransferase (EZH2) may produce more favourable treatment effects. In this study,\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600E<\/jats:sup>\n                    \u2010mutant (BCPAP and K1) and\n                    <jats:italic>BRAF<\/jats:italic>\n                    \u2010wild\u2010type (TPC\u20101) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine\u2010metabolizing genes, radioiodine uptake, and toxicity were tested. We found that tazemetostat alone slightly increased iodine\u2010metabolizing gene expression and promoted radioiodine uptake and toxicity, irrespective of the\n                    <jats:italic>BRAF<\/jats:italic>\n                    status. However, MAPKi induced these effects preferentially in\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600E<\/jats:sup>\n                    mutant cells, which was robustly strengthened by tazemetostat incorporation. Mechanically, MAPKi\u2010induced decrease of trimethylation of H3K27 was evidently intensified by tazemetostat in\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600E<\/jats:sup>\n                    \u2010mutant cells. In conclusion, tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600E<\/jats:sup>\n                    through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.15007","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T23:45:05Z","timestamp":1579736705000},"page":"3336-3345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring\n                    <i>BRAF<\/i>\n                    <sup>V600E<\/sup>\n                    by synergistically decreasing global trimethylation of H3K27"],"prefix":"10.1111","volume":"24","author":[{"given":"Hao","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri","family":"Sa","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital Shanghai 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