miR-190 suppresses breast cancer metastasis by regulation of TGF-β-induced epithelial-mesenchymal transition

Mol Cancer. 2018 Mar 6;17(1):70. doi: 10.1186/s12943-018-0818-9.


Background: Breast cancer is the most common cancer among women worldwide and metastasis is the leading cause of death among patients with breast cancer. The transforming growth factor-β (TGF-β) pathway plays critical roles during breast cancer epithelial-mesenchymal transition (EMT) and metastasis. SMAD2, a positive regulator of TGF-β signaling, promotes breast cancer metastasis through induction of EMT.

Methods: The expression of miR-190 and SMAD2 in breast cancer tissues, adjacent normal breast tissues and cell lines were determined by RT-qPCR. The protein expression levels and localization were analyzed by western blotting and immunofluorescence. ChIP and dual-luciferase report assays were used to validate the regulation of ZEB1-miR-190-SMAD2 axis. The effect of miR-190 on breast cancer progression was investigated both in vitro and in vivo.

Results: miR-190 down-regulation is required for TGF-β-induced EMT. miR-190 suppresses breast cancer metastasis both in vitro and in vivo by targeting SMAD2. miR-190 expression is down-regulated and inversely correlates with SMAD2 in breast cancer samples, and its expression level was associated with outcome in patients with breast cancer. Furthermore, miR-190 is transcriptionally regulated by ZEB1.

Conclusions: Our data uncover the ZEB1-miR-190-SMAD2 axis and provide a mechanism to explain the TGF-β network in breast cancer metastasis.

Keywords: Breast cancer; Epithelial to mesenchymal transition; SMAD2; Transforming growth factor-β; ZEB1; miR-190.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nucleotide Motifs
  • Promoter Regions, Genetic
  • RNA Interference*
  • Signal Transduction
  • Smad2 Protein / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Xenograft Model Antitumor Assays


  • 3' Untranslated Regions
  • MIRN190 microRNA, human
  • MicroRNAs
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta