| 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)
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