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Hokkaido University Collection of Scholarly and Academic Papers >
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MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells
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| Title: | MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells |
| Authors: | Konno, Yosuke Browse this author | | Dong, Peixin Browse this author | | Xiong, Ying Browse this author | | Suzuki, Fumihiko Browse this author →KAKEN DB | | Lu, Jiabin Browse this author | | Cai, Muyan Browse this author | | Watari, Hidemichi Browse this author →KAKEN DB | | Mitamura, Takashi Browse this author | | Hosaka, Masayoshi Browse this author | | Hanley, Sharon J. B. Browse this author →KAKEN DB | | Kudo, Masataka Browse this author | | Sakuragi, Noriaki Browse this author →KAKEN DB |
| Keywords: | microRNA-101 | | proliferation | | EMT | | EZH2 | | MCL-1 | | FOS |
| Issue Date: | 2-Jul-2014 |
| Publisher: | Impact Journals |
| Journal Title: | Oncotarget |
| Volume: | 5 |
| Issue: | 15 |
| Start Page: | 6049 |
| End Page: | 6062 |
| Publisher DOI: | 10.18632/oncotarget.2157 |
| Abstract: | MicroRNA-101 has been implicated as a tumor suppressor miRNA in human tumors. However, its potential functional impact and the underlying mechanisms in endometrial cancer progression have not been determined. Here, we report that in aggressive endometrial cancer cells, re-expression of microRNA-101 leads to inhibition of cell proliferation and induction of apoptosis and senescence. Ectopic overexpression of microRNA-101 attenuates the epithelial-mesenchymal transition-associated cancer cell migration and invasion, abrogates the sphere-forming capacity and enhances chemosensitivity to paclitaxel. Algorithm and microarray-based strategies identifies potential microRNA-101 targets. Among these, we validated EZH2, MCL-1 and FOS as direct targets of miR-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microRNA-101 function. Importantly, further results suggest an inverse correlation between low miR-101 and high EZH2, MCL-1 and FOS expression in EC specimens. We conclude that, as a crucial tumor suppressor, microRNA-101 suppresses cell proliferation, invasiveness and self-renewal in aggressive endometrial cancer cells via modulating multiple critical oncogenes. The microRNA-101-EZH2/MCL-1/FOS axis is a potential therapeutic target for endometrial cancer. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/60536 |
| 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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Submitter: 董 培新
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