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

Oncotarget. 2016 Jan 5;7(1):293-307. doi: 10.18632/oncotarget.6344.


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cisplatin / pharmacology
  • Down-Regulation*
  • Epirubicin / pharmacology
  • Epithelial-Mesenchymal Transition / genetics*
  • Fluorouracil / pharmacology
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Microscopy, Confocal
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antineoplastic Agents
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • MIRN671 microRNA, human
  • MicroRNAs
  • Epirubicin
  • Cisplatin
  • Fluorouracil