EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis

Ihira, Kei; Dong, Peixin; Xiong, Ying; Watari, Hidemichi; Konno, Yosuke; Hanley, Sharon JB; Noguchi, Masayuki; Hirata, Noriyuki; Suizu, Futoshi; Yamada, Takahiro; Kudo, Masataka; Sakuragi, Noriaki

EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis

Ihira, Kei; Dong, Peixin; Xiong, Ying et al.

Oncotarget, 2017, 8(8), 13509-13520

Permalink : https://hdl.handle.net/2115/64562

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アクセス権	open access
URI	https://hdl.handle.net/2115/64562
タイトル	EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis
著者	Ihira, Kei ; Dong, Peixin ; Xiong, Ying ; Watari, Hidemichi ; Konno, Yosuke ; Hanley, Sharon JB ; Noguchi, Masayuki ; Hirata, Noriyuki ; Suizu, Futoshi ; Yamada, Takahiro ; Kudo, Masataka ; Sakuragi, Noriaki
著者名 Ihira, Kei
e-Rad_Researcher 50602504 著者名 Dong, Peixin
著者名 Xiong, Ying
e-Rad_Researcher 10344508 著者名 Watari, Hidemichi
著者名 Konno, Yosuke
e-Rad_Researcher 80529412 著者名 Hanley, Sharon JB
e-Rad_Researcher 40359477 著者名 Noguchi, Masayuki
著者名 Hirata, Noriyuki
e-Rad_Researcher 90431379 著者名 Suizu, Futoshi
e-Rad_Researcher 20419948 著者名 Yamada, Takahiro
著者名 Kudo, Masataka
e-Rad_Researcher 70153963 著者名 Sakuragi, Noriaki
言語	英語
キーワード	EZH2
	GSK343
	miR-361
	endometrial cancer
	5-AZA-CdR
発行日	2017-02-21
出版者	Impact Journals
収録物名	Oncotarget
巻(号)	8(8)
ページ	13509-13520
抄録	EZH2 inhibition and reactivation of tumor suppressor microRNAs (miRNAs) represent attractive anti-cancer therapeutic strategies. We found that EZH2-suppressed let 7b and miR-361, two likely tumor suppressors, inhibited endometrial cancer (EC) cell proliferation and invasion, and abrogated cancer stem cell-like properties. In EC cells, EZH2 induced and functioned together with YY1 to epigenetically suppress miR-361, which upregulated Twist, a direct target of miR-361. Treating EC cells with GSK343, a specific EZH2 inhibitor, mimicked the effects of siRNA-mediated EZH2 knockdown, upregulating miR-361 and downregulating Twist expression. Combining GSK343 with 5 AZA-2’-deoxycytidine synergistically suppressed cell proliferation and invasion in vitro, and decreased tumor size and weight in EC cell xenografted mice. Quantitative real-time PCR analysis of 24 primary EC tissues showed that lower let-7b and miR-361 levels were associated with worse patient outcomes. These results were validated in a larger EC patient dataset from The Cancer Genome Atlas. Our findings suggest that EZH2 drives EC progression by regulating miR-361/Twist signaling, and support EZH2 inhibition as a promising anti-EC therapeutic strategy.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1949-2553
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.18632/oncotarget.14586