Estrogen receptor-α-miR-1271-SNAI2 feedback loop regulates transforming growth factor-β-induced breast cancer progression

J Exp Clin Cancer Res. 2019 Mar 1;38(1):109. doi: 10.1186/s13046-019-1112-4.


Background: Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-α (ERα) or/and progesterone receptor. ERα has been identified to promote the growth of primary breast cancer, however, it can also antagonize signaling pathways that lead to epithelial-mesenchymal transition (EMT), including transforming growth factor-β (TGF-β) signaling. miRNA alteration or dysfunction is involved in cancer development and progression. Although miR-1271 has identified as a tumor suppressor in various cancers, the role of miR-1271 in breast cancer is still limited.

Methods: The effect of miR-1271 on breast cancer progression was investigated both in vitro and in vivo. The EMT-related protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to validate the regulation of ERα-miR-1271-SNAI2 feedback loop.

Results: miR-1271 suppresses breast cancer progression and EMT phenotype both in vitro and in vivo by targeting SNAI2. Estrogen reverses TGF-β-induced EMT in a miR-1271 dependent manner. Furthermore, ERα transactivates the miR-1271 expression and is also transcriptionally repressed by SNAI2.

Conclusions: Our data uncover the ERα-miR-1271-SNAI2 feedback loop and provide a mechanism to explain the TGF-β network in breast cancer progression.

Keywords: Breast cancer; ERα; Epithelial to mesenchymal transition; SNAI2; Transforming growth factor-β; miR-1271.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / physiology
  • Estrogen Receptor alpha / metabolism*
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Snail Family Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MIRN1271 microRNA, human
  • MicroRNAs
  • SNAI2 protein, human
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta