MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.

Yosuke Konno; Peixin Dong; Ying Xiong; Fumihiko Suzuki; Jiabin Lu; Muyan Cai; Hidemichi Watari; Takashi Mitamura; Masayoshi Hosaka; Sharon J. B. Hanley; Masataka Kudo; Noriaki Sakuragi

doi:10.18632/oncotarget.2157

MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.

Yosuke Konno^* (Corresponding Author), Peixin Dong, Ying Xiong, Fumihiko Suzuki, Jiabin Lu, Muyan Cai, Hidemichi Watari, Takashi Mitamura, Masayoshi Hosaka, Sharon J. B. Hanley, Masataka Kudo, Noriaki Sakuragi

^*Corresponding author for this work

Applied Health Sciences

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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.

Original language	English
Pages (from-to)	6049-6062
Number of pages	14
Journal	Oncotarget
Volume	5
Issue number	15
Early online date	2 Jul 2014
DOIs	https://doi.org/10.18632/oncotarget.2157
Publication status	Published - 2 Jul 2014

Bibliographical note

ACKNOWLEDGEMENTS
This work was funded by a grant from the Department of Women’s Health Educational System, a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan, and a Grant-in-Aid for Scientific Research (C) (24592496). We thank Dr. Zhujie Xu for excellent technical assistance.

Keywords

micorRNA-101
proliferation
EMT
EZH2
MCL-1
FOS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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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.",

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.",

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author = "Yosuke Konno and Peixin Dong and Ying Xiong and Fumihiko Suzuki and Jiabin Lu and Muyan Cai and Hidemichi Watari and Takashi Mitamura and Masayoshi Hosaka and Hanley, {Sharon J. B.} and Masataka Kudo and Noriaki Sakuragi",

note = "ACKNOWLEDGEMENTS This work was funded by a grant from the Department of Women{\textquoteright}s Health Educational System, a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan, and a Grant-in-Aid for Scientific Research (C) (24592496). We thank Dr. Zhujie Xu for excellent technical assistance.",

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AU - Konno, Yosuke

AU - Dong, Peixin

AU - Xiong, Ying

AU - Suzuki, Fumihiko

AU - Lu, Jiabin

AU - Cai, Muyan

AU - Watari, Hidemichi

AU - Mitamura, Takashi

AU - Hosaka, Masayoshi

AU - Hanley, Sharon J. B.

AU - Kudo, Masataka

AU - Sakuragi, Noriaki

N1 - ACKNOWLEDGEMENTS This work was funded by a grant from the Department of Women’s Health Educational System, a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan, and a Grant-in-Aid for Scientific Research (C) (24592496). We thank Dr. Zhujie Xu for excellent technical assistance.

PY - 2014/7/2

Y1 - 2014/7/2

N2 - 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.

AB - 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.

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KW - proliferation

KW - EMT

KW - EZH2

KW - MCL-1

KW - FOS

U2 - 10.18632/oncotarget.2157

DO - 10.18632/oncotarget.2157

M3 - Article

SN - 1949-2553

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JF - Oncotarget

IS - 15

ER -

MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.

Abstract

Bibliographical note

Keywords

UN SDGs

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