TY - JOUR
T1 - FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway
AU - Kottakis, Filippos
AU - Polytarchou, Christos
AU - Foltopoulou, Parthena
AU - Sanidas, Ioannis
AU - Kampranis, Sotirios
AU - Tsichlis, Philip N
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/7/22
Y1 - 2011/7/22
N2 - 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 an oncogenic pathway that functionally links FGF-2 with EZH2 via NDY1 and miR-101.
AB - 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 an oncogenic pathway that functionally links FGF-2 with EZH2 via NDY1 and miR-101.
KW - Animals
KW - Cell Line, Tumor
KW - Cell Movement
KW - Cell Proliferation
KW - DNA-Binding Proteins
KW - F-Box Proteins
KW - Fibroblast Growth Factor 2
KW - Histone Demethylases
KW - Histone-Lysine N-Methyltransferase
KW - Humans
KW - Jumonji Domain-Containing Histone Demethylases
KW - Mice
KW - MicroRNAs
KW - Neovascularization, Physiologic
KW - Oxidoreductases, N-Demethylating
KW - Polycomb Repressive Complex 2
KW - Transcription Factors
U2 - 10.1016/j.molcel.2011.06.020
DO - 10.1016/j.molcel.2011.06.020
M3 - Journal article
C2 - 21777817
SN - 1097-2765
VL - 43
SP - 285
EP - 298
JO - Molecular Cell
JF - Molecular Cell
IS - 2
ER -
