Resveratrol Limits Epithelial to Mesenchymal Transition Through Modulation of Khsrp/Hnrnpa1-Dependent Alternative Splicing in Mammary Gland Cells Publisher Pubmed



Moshiri A^{1, 2, 3} ; Puppo M^{1, 3} ; Rossi M^{1, 3} ; Gherzi R¹ ; Briata P¹ Show Affiliations
Source: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms Published:2017

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. © 2017 Elsevier B.V.