Oncotarget

Research Papers:

miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer

Xiaohui Tan, Yebo Fu, Liang Chen, Woojin Lee, Yinglei Lai, Katayoon Rezaei, Sana Tabbara, Patricia Latham, Christine B. Teal, Yan-Gao Man, Robert S. Siegel, Rachel F. Brem & Sidney W. Fu _

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Oncotarget. 2016; 7:293-307. https://doi.org/10.18632/oncotarget.6344

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Abstract

Xiaohui Tan1, Yebo Fu1, Liang Chen1, Woojin Lee1, Yinglei Lai2, Katayoon Rezaei3, Sana Tabbara3, Patricia Latham3, Christine B. Teal4, Yan-Gao Man5, Robert S. Siegel6, Rachel F. Brem7, Sidney W. Fu1

1Department of Medicine (Division of Genomic Medicine), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

2Department of Statistics, The George Washington University, Washington, DC, USA

3Department of Pathology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

4Department of Surgery, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

5Research Lab and International Collaboration, Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA, USA

6Department of Medicine (Division of Hematology/Oncology), The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

7Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

Correspondence to:

Sidney W. Fu, e-mail: sfu@gwu.edu

Keywords: breast cancer, miR-671-5p, tumor suppressor, FOXM1, EMT

Received: August 31, 2015    Accepted: November 11, 2015    Published: November 18, 2015

ABSTRACT

MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.


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