MiR-204-5p/Six1 feedback loop promotes epithelial-mesenchymal transition in breast cancer

Tumour Biol. 2016 Feb;37(2):2729-35. doi: 10.1007/s13277-015-4039-1. Epub 2015 Sep 25.

Abstract

Epithelial-mesenchymal transition (EMT) is a vital process in epithelial cancer invasion and metastasis. The induction of EMT by Six1 has been described as a common mode of cancer progression, which could promote breast cancer migration and invasion. In the study, we found that miR-204-5p could suppress the migration and invasion of breast cancer cell lines. Since overexpression of Six1 promote EMT, we identified a mechanism by which miR-204-5p inhibited the EMT by downregulating the Six1, which was mediated by a conserved miR-204-5p seed-matching sequence in the 3'-UTR of Six1 mRNA. We also identified that upregulation of Six1 could downregulate miR-204-5p expression, affecting the migration and invasion of breast cancer cell lines. In conclusion, the frequent upregulation of Six1 and/or downregulation of miR-204-5p in breast cancer may shift the equilibrium of these reciprocal regulations and lock breast cancer cells in the mesenchymal state.

Keywords: Breast cancer; EMT; Six1; miR-204-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • Homeodomain Proteins / genetics*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • Homeodomain Proteins
  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • SIX1 protein, human