EZH2 and KDM6B Expressions Are Associated with Specific Epigenetic Signatures during EMT in Non Small Cell Lung Carcinomas

EZH2 和 KDM6B 表达与非小细胞肺癌 EMT 过程中的特定表观遗传特征相关

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作者:Camille Lachat, Diane Bruyère, Amandine Etcheverry, Marc Aubry, Jean Mosser, Walid Warda, Michaël Herfs, Elodie Hendrick, Christophe Ferrand, Christophe Borg, Régis Delage-Mourroux, Jean-Paul Feugeas, Michaël Guittaut, Eric Hervouet, Paul Peixoto

Abstract

The role of Epigenetics in Epithelial Mesenchymal Transition (EMT) has recently emerged. Two epigenetic enzymes with paradoxical roles have previously been associated to EMT, EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 (PRC2) Subunit), a lysine methyltranserase able to add the H3K27me3 mark, and the histone demethylase KDM6B (Lysine Demethylase 6B), which can remove the H3K27me3 mark. Nevertheless, it still remains unclear how these enzymes, with apparent opposite activities, could both promote EMT. In this study, we evaluated the function of these two enzymes using an EMT-inducible model, the lung cancer A549 cell line. ChIP-seq coupled with transcriptomic analysis showed that EZH2 and KDM6B were able to target and modulate the expression of different genes during EMT. Based on this analysis, we described INHBB, WTN5B, and ADAMTS6 as new EMT markers regulated by epigenetic modifications and directly implicated in EMT induction.

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