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

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Title: EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis
Authors: Ihira, Kei Browse this author
Dong, Peixin Browse this author →KAKEN DB
Xiong, Ying Browse this author
Watari, Hidemichi Browse this author →KAKEN DB
Konno, Yosuke Browse this author
Hanley, Sharon JB Browse this author →KAKEN DB
Noguchi, Masayuki Browse this author →KAKEN DB
Hirata, Noriyuki Browse this author
Suizu, Futoshi Browse this author →KAKEN DB
Yamada, Takahiro Browse this author →KAKEN DB
Kudo, Masataka Browse this author
Sakuragi, Noriaki Browse this author →KAKEN DB
Keywords: EZH2
GSK343
miR-361
endometrial cancer
5-AZA-CdR
Issue Date: 21-Feb-2017
Publisher: Impact Journals
Journal Title: Oncotarget
Volume: 8
Issue: 8
Start Page: 13509
End Page: 13520
Publisher DOI: 10.18632/oncotarget.14586
Abstract: 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.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/64562
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 董 培新

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