Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties.
Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties.
复制标题
DOI：
10.1038/srep02687
复制
发表时间：
2013
影响因子：
4.6
通讯作者：
Mani, Sendurai A.
中科院分区：
文献类型：
--
作者：
Taube, Joseph H.;Malouf, Gabriel G.;Lu, Emily;Sphyris, Nathalie;Vijay, Vidya;Ramachandran, Priyanka P.;Ueno, Katumasa R.;Gaur, Sanchaika;Nicoloso, Milena S.;Rossi, Simona;Herschkowitz, Jason I.;Rosen, Jeffrey M.;Issa, Jean-Pierre J.;Calin, George A.;Chang, Jeffrey T.;Mani, Sendurai A.
上皮-间充质转化（EMT）通过减少细胞间粘附、增加迁移能力、干细胞特性和失巢凋亡以及化疗抗性赋予原本非转移性癌细胞转移能力。在这项研究中，我们分析了EMT过程中microRNA表达的变化，以及microRNA启动子DNA甲基化的变化，以发现EMT赋予的干性特性的基本介质。MicroRNA-203（miR-203）表达在由多种不同刺激诱导的EMT后以及在建立的封闭蛋白低细胞系以及富含CD 44 hi/CD 24 lo干细胞的级分中被抑制。miR-203在间充质细胞中的表达损害了体外迁移和侵袭能力，以及体内肿瘤的发生和转移。出乎意料的是，miR-203表达通过间接增强DKK 1的表达影响邻近细胞的球体形成能力，DKK 1是Wnt信号传导和干性的分泌抑制剂，导致β-连环蛋白水平的抑制。我们的数据表明，恢复miR-203表达水平可能会抑制转移和打击失调的Wnt信号。
The epithelial-mesenchymal transition (EMT) imparts metastatic competence on otherwise non-metastatic cancer cells through decreased inter-cellular adhesions, increased migratory capacity, stem cell properties and anoikis and chemotherapy resistance. In this study, we profiled changes in microRNA expression during EMT in conjunction with changes in DNA methylation at microRNA promoters to discover essential mediators of EMT-imparted stemness properties. MicroRNA-203 (miR-203) expression is repressed following EMT induced by multiple different stimuli and in established claudin-low cell lines as well as the CD44hi/CD24lo stem cell-enriched fraction. Expression of miR-203 in mesenchymal cells compromises migratory and invasive capacity in vitro, and tumor initiation and metastasis in vivo. Unexpectedly, miR-203 expression affects the sphere-forming capacity of neighboring cells by indirectly enhancing expression of DKK1, a secreted inhibitor of Wnt signaling and stemness resulting in suppression of β-catenin protein levels. Our data suggest that restoring miR-203 expression levels may inhibit metastasis and combat deregulated Wnt signaling.
登录
查看更多内容
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
3.7
作者：
Li Y;Lu W;King TD;Liu CC;Bijur GN;Bu G
通讯作者：
Bu G
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
9.7
作者：
Kanai, Y;Ushijima, S;Hirohashi, S
通讯作者：
Hirohashi, S
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C