Oncotarget

Research Papers:

miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation

Peixin Dong _, Ying Xiong, Junming Yue, Sharon J.B. Hanley and Hidemichi Watari

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Oncotarget. 2018; 9:23253-23263. https://doi.org/10.18632/oncotarget.25298

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Abstract

Peixin Dong1,*, Ying Xiong2,*, Junming Yue3,4, Sharon J.B. Hanley5 and Hidemichi Watari1

1Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan

2Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

3Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

4Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA

5Department of Women’s Health Educational System, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan

*These authors contributed equally to this work

Correspondence to:

Peixin Dong, email: [email protected]

Hidemichi Watari, email: [email protected]

Keywords: microRNA-34a; microRNA-424; microRNA-513; MMSET; endometrial cancer metastasis

Received: March 24, 2018     Accepted: April 16, 2018     Published: May 01, 2018

ABSTRACT

Although the oncogene MMSET (also known as NSD2 or WHSC1) has an essential role in malignancies, its impact on human endometrial cancer (EC) metastasis and the molecular mechanism of MMSET regulation are largely unknown. We report that MMSET was markedly upregulated in EC cell lines and EC tissues, and was significantly associated with poor survival in EC. MMSET overexpression greatly promoted EC cell invasion and sphere formation, whereas inhibition of MMSET reduced EC cell invasion and sphere formation. Importantly, Twist1 was required for MMSET-induced EC cell invasion and sphere formation. Moreover, we demonstrate that miR-34a, miR-424 and miR-513 directly modulate MMSET expression to attenuate the invasion and sphere formation capacity of EC cells. miR-34a, miR-424 and miR-513 were down-regulated in EC compared with normal tissue, and reduced expression of miR-34a, miR-424 and miR-513 was clinically associated with a poorer prognosis in EC patients. Furthermore, specific inhibition of MMET with BIX-01294 led to decreased EC cell invasion and impaired sphere formation. These findings suggest a pro-metastatic role for MMSET in EC and reveal that the repression of miR-34a, miR-424 and miR-513 contributes to the overexpression of MMSET during EC metastasis.


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