Signaling between transforming growth factor β (TGF-β) and transcription factor snai2 represses expression of Microrna mir-203 to promote epithelial-Mesenchymal transition and tumor metastasis

Xiangming Ding, Serk In Park, Laurie K. McCauley, Cun Yu Wang

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

TGF-β promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). Understanding the molecular and epigenetic mechanisms by which TGF-β inducesEMTmay facilitate the development of new therapeutic strategies for metastasis. Here, we report that TGF-β induced SNAI2 to promote EMT by repressing miR-203. Although miR- 203 targeted SNAI2, SNAI2 induced by TGF-β could directly bind to the miR-203 promoter to inhibit its transcription. SNAI2 and miR-203 formed a double negative feedback loop to inhibit each other's expression, thereby controlling EMT. Moreover, we found that miR-203 was significantly down-regulated in highly metastatic breast cancer cells. The restoration of miR- 203 in highly metastatic breast cancer cells inhibited tumor cell invasion in vitro and lung metastatic colonization in vivo by repressing SNAI2. Taken together, our results suggest that the SNAI2 and miR-203 regulatory loop plays important roles in EMT and tumor metastasis.

Original languageEnglish
Pages (from-to)10241-10253
Number of pages13
JournalJournal of Biological Chemistry
Volume288
Issue number15
DOIs
Publication statusPublished - 2013 Apr 12

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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