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

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. © 2014 The Authors. Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.