Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
Volume 1860, Issue 3, Pages 291-298Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagrm.2017.01.001
Keywords
Epithelial to mesenchymal transition; Resveratrol; Alternative splicing; RNA-Binding Proteins
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [15195]
- Italian Ministero della Salute 5xmille [S361A]
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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-beta-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 hnRNPAl. 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. (C) 2017 Elsevier B.V. All rights reserved.
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