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

Authors

Xiaohui Tan, School of Medicine and Health Sciences
Yebo Fu, School of Medicine and Health Sciences
Liang Chen, School of Medicine and Health Sciences
Woojin Lee, School of Medicine and Health Sciences
Yinglei Lai, The George Washington University
Katayoon Rezaei, School of Medicine and Health Sciences
Sana Tabbara, School of Medicine and Health Sciences
Patricia Latham, School of Medicine and Health Sciences
Christine B. Teal, School of Medicine and Health Sciences
Yan Gao Man, Research Lab and International Collaboration
Robert S. Siegel, School of Medicine and Health Sciences
Rachel F. Brem, School of Medicine and Health Sciences
Sidney W. Fu, School of Medicine and Health Sciences

Document Type

Journal Article

Publication Date

1-1-2016

Journal

Oncotarget

Volume

7

Issue

1

DOI

10.18632/ONCOTARGET.6344

Keywords

Breast cancer; EMT; FOXM1; MiR-671-5p; Tumor suppressor

Abstract

© 2015. Oncotarget. 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.

APA Citation

Tan, X., Fu, Y., Chen, L., Lee, W., Lai, Y., Rezaei, K., Tabbara, S., Latham, P., Teal, C., Man, Y., Siegel, R., Brem, R., & Fu, S. (2016). miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer. Oncotarget, 7 (1). http://dx.doi.org/10.18632/ONCOTARGET.6344