B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA methyltransferase 1.
B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA methyltransferase 1.
复制标题
B-RAFV600E通过调节DNA甲基转移酶1抑制碘化钠的表达。
DOI：
10.1038/emm.2014.68
复制
发表时间：
2014-11-07
影响因子：
12.8
通讯作者：
Park, Tae Jun
中科院分区：
文献类型：
--
作者：
Choi, Yong Won;Kim, Hyun-Ju;Kim, Young Hwa;Park, So Hyun;Chwae, Yong Jun;Lee, Jeonghun;Soh, Euy Young;Kim, Jang-Hee;Park, Tae Jun
B-RafV600E 突变体存在于 40-70% 的甲状腺乳头状癌 (PTC) 中，在 PTC 的发病机制中具有重要作用。碘化钠同向转运蛋白 (NIS) 是一种完整的质膜糖蛋白，可介导主动碘化物转运至甲状腺滤泡细胞中，已知 B-RafV600E 与 NIS 表达缺失有关。在本研究中，我们发现B-RafV600E通过上调其启动子甲基化来抑制NIS表达，并且与周围正常组织相比，携带PTC的B-RafV600E中NIS启动子的CpG岛的特定区域高度甲基化。尽管 B-RafV600E 不会增加 DNA 甲基转移酶 3a 和 3b (DNMT3a,3b)，但表达 PTC 和 B-RafV600E 的甲状腺细胞中 DNMT1 表达显着上调。此外，B-RafV600E 诱导的 NF-κB 激活上调了 DNMT1 表达。这些结果使我们得出结论，B-RafV600E 诱导的 NIS 启动子甲基化是 PTC 中 NIS 下调的可能机制之一。
B-RafV600E mutant is found in 40–70% of papillary thyroid carcinoma (PTC) and has an important role in the pathogenesis of PTC. The sodium iodide symporter (NIS) is an integral plasma membrane glycoprotein that mediates active iodide transport into the thyroid follicular cells, and B-RafV600E has been known to be associated with the loss of NIS expression. In this study, we found that B-RafV600E inhibited NIS expression by the upregulation of its promoter methylation, and that specific regions of CpG islands of NIS promoter in B-RafV600E harboring PTC were highly methylated compared with surrounding normal tissue. Although DNA methyltransferase 3a and 3b (DNMT3a,3b) were not increased by B-RafV600E, DNMT1 expression was markedly upregulated in PTC and B-RafV600E expressing thyrocytes. Furthermore, DNMT1 expression was upregulated by B-RafV600E induced NF-κB activation. These results led us to conclude that NIS promoter methylation, which was induced by B-RafV600E, is one of the possible mechanisms involved in NIS downregulation in PTC.
登录
查看更多内容
影响因子：
5.8
作者：
Arturi, F;Russo, D;Filetti, S
通讯作者：
Filetti, S
影响因子：
4.7
作者：
Peng, Dun-Fa;Kanai, Yae;Hirohashi, Setsuo
通讯作者：
Hirohashi, Setsuo
DOI：
10.1016/0006-291x(91)91540-s
发表时间：
1991-02-14
影响因子：
3.1
作者：
OHTA, K;ENDO, T;ONAYA, T
通讯作者：
ONAYA, T
影响因子：
13.5
作者：
Kogai, Takahiko;Brent, Gregory A.
通讯作者：
Brent, Gregory A.
影响因子：
3.7
作者：
Galrao, A. L.;Sodre, A. K.;Rubio, I. G. S.
通讯作者：
Rubio, I. G. S.