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

Xiaohui Tan1, Yebo Fu1, Liang Chen1

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

Oncotarget
|November 21, 2015
PubMed

Insights

MicroRNA miR-671-5p acts as a tumor suppressor in breast cancer by targeting FOXM1. Its reduced expression in invasive ductal carcinoma suggests potential as a therapeutic target for breast cancer management.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA (miRNA) dysfunction is implicated in human diseases, including cancer.
  • Previous research indicated miR-671-5p dysregulation during breast cancer progression.
  • This study investigates the specific role of miR-671-5p in breast tumorigenesis.

Purpose of the Study:

  • To elucidate the function of miR-671-5p in breast cancer.
  • To identify direct targets of miR-671-5p involved in tumorigenesis.
  • To explore the therapeutic potential of miR-671-5p in breast cancer management.

Main Methods:

  • Analysis of miR-671-5p expression in invasive ductal carcinoma (IDC) tissues.
  • Luciferase assays to confirm direct targeting of Forkhead Box M1 (FOXM1).
  • In vitro experiments involving forced expression of miR-671-5p in breast cancer cell lines, including proliferation, invasion, EMT/MET transition, cell cycle, and drug sensitivity assays.
  • Host cell reactivation (HCR) assays to assess DNA repair capability.
  • cDNA microarray analysis to identify differentially expressed genes.

Main Results:

  • miR-671-5p expression was significantly decreased in IDC tissues compared to normal tissues.
  • FOXM1 was confirmed as a direct target of miR-671-5p.
  • Forced miR-671-5p expression suppressed breast cancer cell proliferation and invasion, induced S-phase arrest, and promoted a shift from EMT to MET phenotypes.
  • miR-671-5p sensitized cells to chemotherapy drugs (cisplatin, 5-FU, epirubicin) and reduced DNA repair capacity.
  • Gene expression profiling revealed miR-671-5p affects pathways related to cell proliferation, invasion, cell cycle, and EMT.

Conclusions:

  • miR-671-5p functions as a tumor suppressor miRNA in breast cancer, primarily by targeting the oncogenic transcription factor FOXM1.
  • Restoring miR-671-5p levels inhibits tumor growth, metastasis, and enhances chemosensitivity.
  • miR-671-5p represents a promising novel therapeutic target for breast cancer treatment.

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