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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)293-307
Number of pages15
JournalOncotarget
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

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

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Tan, X., Fu, Y., Chen, L., Lee, W., Lai, Y., Rezaei, K., Tabbara, S., Latham, P., Teal, C. B., Man, Y. G., Siegel, R. S., Brem, R. F., & Fu, S. W. (2016). miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer. Oncotarget, 7(1), 293-307. https://doi.org/10.18632/ONCOTARGET.6344