EED regulates epithelial-mesenchymal transition of cancer cells induced by TGF-β

Dulamsuren Oktyabri; Shoichiro Tange; Minoru Terashima; Akihiko Ishimura; Takeshi Suzuki

doi:10.1016/j.bbrc.2014.09.082

EED regulates epithelial-mesenchymal transition of cancer cells induced by TGF-β

Biochem Biophys Res Commun. 2014 Oct 10;453(1):124-30. doi: 10.1016/j.bbrc.2014.09.082. Epub 2014 Sep 26.

Authors

Dulamsuren Oktyabri¹, Shoichiro Tange¹, Minoru Terashima¹, Akihiko Ishimura¹, Takeshi Suzuki²

Affiliations

¹ Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
² Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan. Electronic address: suzuki-t@staff.kanazawa-u.ac.jp.

PMID: 25264103
DOI: 10.1016/j.bbrc.2014.09.082

Abstract

Histone methylation is involved in various biological and pathological processes including cancer development. In this study, we found that EED, a component of Polycomb repressive complex-2 (PRC2) that catalyzes methylation of lysine 27 of histone H3 (H3K27), was involved in epithelial-mesenchymal transition (EMT) of cancer cells induced by Transforming Growth Factor-beta (TGF-β). The expression of EED was increased during TGF-β-induced EMT and knockdown of EED inhibited TGF-β-induced morphological conversion of the cells associated with EMT. EED knockdown antagonized TGF-β-dependent expression changes of EMT-related genes such as CDH1, ZEB1, ZEB2 and microRNA-200 (miR-200) family. Chromatin immunoprecipitation assays showed that EED was implicated in TGF-β-induced transcriptional repression of CDH1 and miR-200 family genes through the regulation of histone H3 methylation and EZH2 occupancies on their regulatory regions. Our study demonstrated a novel role of EED, which regulates PRC2 activity and histone methylation during TGF-β-induced EMT of cancer cells.

Keywords: Cancer progression; Epithelial–mesenchymal transition; Histone methylation; Transcriptional regulation; microRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, CD
Cadherins / genetics
Cell Line, Tumor
Epithelial-Mesenchymal Transition / genetics
Epithelial-Mesenchymal Transition / physiology*
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HT29 Cells
Histones / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Humans
MicroRNAs / genetics
Neoplasms / genetics
Neoplasms / pathology*
Neoplasms / physiopathology*
Polycomb Repressive Complex 2 / antagonists & inhibitors
Polycomb Repressive Complex 2 / genetics
Polycomb Repressive Complex 2 / physiology*
Promoter Regions, Genetic
Repressor Proteins / genetics
Repressor Proteins / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Transforming Growth Factor beta / physiology*
Zinc Finger E-box Binding Homeobox 2
Zinc Finger E-box-Binding Homeobox 1

Substances

Antigens, CD
CDH1 protein, human
Cadherins
EED protein, human
Histones
Homeodomain Proteins
MIRN200 microRNA, human
MicroRNAs
Repressor Proteins
Transcription Factors
Transforming Growth Factor beta
ZEB1 protein, human
ZEB2 protein, human
Zinc Finger E-box Binding Homeobox 2
Zinc Finger E-box-Binding Homeobox 1
Polycomb Repressive Complex 2