miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer
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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
Sidney W. Fu, e-mail: firstname.lastname@example.org
Keywords: breast cancer, miR-671-5p, tumor suppressor, FOXM1, EMT
Received: August 31, 2015 Accepted: November 11, 2015 Published: November 18, 2015
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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