FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway.
FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway.
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DOI：
10.1016/j.molcel.2011.06.020
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发表时间：
2011-07-22
期刊：
影响因子：
16
通讯作者：
Tsichlis PN
中科院分区：
文献类型：
--
作者：
Kottakis F;Polytarchou C;Foltopoulou P;Sanidas I;Kampranis SC;Tsichlis PN
组蛋白H3K27甲基转移酶EZH2在肿瘤发生中起重要作用，其作用机制尚不完全清楚。在这里，我们证明了JmjC结构域组蛋白H3去甲基酶NDY1与EZH2协同作用，使EZH2抑制剂miR-101沉默。NDY1和EZH2通过NDY1上调触发的过程协同结合其启动子来抑制miR-101。虽然EZH2结合依赖于NDY1，但后者独立于EZH2结合。然而，这两种基因都需要抑制转录。NDY1和EZH2协同作用，上调EZH2，稳定miR-101的抑制及其结局。NDY1是由成纤维细胞生长因子-2通过激活CREB在DYRK1a下游诱导的，并介导成纤维细胞生长因子-2和EZH2对细胞的增殖、迁移和血管生成的影响。本文所述的成纤维细胞生长因子-2-NDY1/EZH2-miR-101-EZH2轴在膀胱癌中被发现是活跃的。这些数据描绘了一条新的致癌途径，该途径通过NDY1和miR-101在功能上将FGF-2与EZH2连接起来。
The histone H3K27 methyltransferase EZH2 plays an important role in oncogenesis, by mechanisms that are incompletely understood. Here we show that the JmjC domain histone H3 demethylase NDY1 synergizes with EZH2 to silence the EZH2 inhibitor miR-101. NDY1 and EZH2 repress miR-101 by binding its promoter in concert, via a process triggered by upregulation of NDY1. Whereas EZH2 binding depends on NDY1, the latter binds independently of EZH2. However, both are required to repress transcription. NDY1 and EZH2 acting in concert, upregulate EZH2 and stabilize the repression of miR-101 and its outcome. NDY1 is induced by FGF-2 via CREB phosphorylation and activation, downstream of DYRK1A, and mediates the FGF-2 and EZH2 effects on cell proliferation, migration and angiogenesis. The FGF-2-NDY1/EZH2-miR-101-EZH2 axis described here, was found to be active in bladder cancer. These data delineate a novel oncogenic pathway that functionally links FGF-2 with EZH2 via NDY1 and miR-101.
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影响因子：
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