Reference - Detail
| RRC ID | 65117 |
|---|---|
| Author | Ihira K, Dong P, Xiong Y, Watari H, Konno Y, Hanley SJ, Noguchi M, Hirata N, Suizu F, Yamada T, Kudo M, Sakuragi N. |
| Title | EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis. |
| Journal | Oncotarget |
| 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. |
| Volume | 8(8) |
| Pages | 13509-13520 |
| Published | 2017-2-21 |
| DOI | 10.18632/oncotarget.14586 |
| PII | 14586 |
| PMID | 28088786 |
| PMC | PMC5355116 |
| MeSH | Animals Cell Line, Tumor Disease Progression Endometrial Neoplasms / drug therapy* Endometrial Neoplasms / genetics Endometrial Neoplasms / metabolism Endometrial Neoplasms / pathology Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors* Enhancer of Zeste Homolog 2 Protein / genetics Enhancer of Zeste Homolog 2 Protein / metabolism Enzyme Inhibitors / pharmacology* Female Humans Indazoles / pharmacology* Mice Mice, Inbred BALB C MicroRNAs / metabolism* Nuclear Proteins / metabolism* Pyridones / pharmacology* Transfection Twist-Related Protein 1 / metabolism* Xenograft Model Antitumor Assays |
| IF | 5.168 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Wikipedia |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HOUA-I(RCB0659) |