Suppression of the TGF-β1-induced protein expression of SNAI1 and N-cadherin by miR-199a

Genes Cells. 2014 Sep;19(9):667-75. doi: 10.1111/gtc.12166. Epub 2014 Jul 10.

Abstract

MicroRNA miR-199a is clustered with miR-214 on chromosome 1 and its expression is up-regulated by various factors that are associated with epithelial-to-mesenchymal transition (EMT), such as a transcriptional repressor Twist1 and transforming growth factor (TGF)-β. miR-199a is either up-regulated or down-regulated in a variety of cancers, although EMT is associated with the progression of cancer. We found here that miR-199a suppressed the translation of SNAI1, a transcriptional repressor that plays a role in EMT, by targeting the sequence within the 3'UTR of the SNAI1 mRNA, and reduced the protein level of SNAI1. miR-199a increased the protein level of claudin-1 in both the TGF-β1-treated and -untreated cells at least partly by decreasing the protein level of SNAI1, a transcriptional repressor for claudin-1. In addition, miR-199a targeted the sequence within the 3'UTR of the N-cadherin mRNA and suppressed the TGF-β1-induced increase in the protein level of N-cadherin in a manner independent of SNAI1. These results indicate that miR-199a suppresses the TGF-β1-induced protein expression of SNAI1 and N-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Claudin-1 / genetics
  • Claudin-1 / metabolism
  • Down-Regulation*
  • Humans
  • MicroRNAs / metabolism*
  • Snail Family Transcription Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Cadherins
  • Claudin-1
  • MicroRNAs
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transcription Factors
  • Transforming Growth Factor beta1
  • mirn199 microRNA, human