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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)

Submitter: 董 培新

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