Resveratrol limits epithelial to mesenchymal transition through modulation of KHSRP/hnRNPA1-dependent alternative splicing in mammary gland cells

Arfa Moshiri, Margherita Puppo, Martina Rossi, Roberto Gherzi, Paola Briata

Research output: Contribution to journalArticle

Abstract

Resveratrol (RESV) is a natural polyphenolic compound endowed with anti-inflammatory, anti-proliferative, as well as pro-apoptotic activities that make it a potential anti-tumor compound. Here we show that RESV counteracts the TGF-β-induced Epithelial to Mesenchymal Transition (EMT) phenotype in mammary gland cells and affects the alternative exon usage of pre-mRNAs that encode crucial factors in adhesion and migration —including CD44, ENAH, and FGFR2— in a panel of immortalized and transformed mammary gland cells. RESV causes a shift from the mesenchymal-specific forms of these factors to the respective epithelial forms and increases the expression of the RNA-binding proteins KHSRP and hnRNPA1. From a mechanistic point of view, we show that the combined silencing of KHSRP and hnRNPA1 prevents the RESV-dependent inclusion of the epithelial-type exons in the Cd44 pre-mRNA. Our findings support an unexpected regulatory mechanism where RESV limits EMT by controlling gene expression at post-transcriptional level.

Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1860
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

Keywords

  • Alternative splicing
  • Epithelial to mesenchymal transition
  • Resveratrol
  • RNA-Binding Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics

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