Epithelial-to-mesenchymal transition (EMT) confers several traits to cancer cells that are required for malignant progression. Here, we report that miR-27b-3p-mediated silencing of the single-strand RNA binding protein KHSRP is required for transforming growth factor β (TGF-β)-induced EMT in mammary gland cells. Sustained KHSRP expression limits TGF-β-dependent induction of EMT factors and cell migration, whereas its knockdown in untreated cells mimics TGF-β-induced EMT. Genome-wide sequencing analyses revealed that KHSRP controls (1) levels of mature miR-192-5p, a microRNA that targets a group of EMT factors, and (2) alternative splicing of a cohort of pre-mRNAs related to cell adhesion and motility including Cd44 and Fgfr2. KHSRP belongs to a ribonucleoprotein complex that includes hnRNPA1, and the two proteins cooperate in promoting epithelial-type exon usage of select pre-mRNAs. Thus, TGF-β-induced KHSRP silencing is central in a pathway leading to gene-expression changes that contribute to the cellular changes linked to EMT.
miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-β-Induced Epithelial-to-Mesenchymal Transition / M. Puppo, G. Bucci, M. Rossi, M. Giovarelli, D. Bordo, A. Moshiri, F. Gorlero, R. Gherzi, P. Briata. - In: CELL REPORTS. - ISSN 2211-1247. - 16:4(2016 Jul 26), pp. 967-978.
|Titolo:||miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-β-Induced Epithelial-to-Mesenchymal Transition|
BUCCI, GABRIELE (Secondo)
|Parole Chiave:||Alternative Splicing; Animals; Cell Adhesion; Cell Line; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Hyaluronan Receptors; Mammary Glands, Animal; Mice; MicroRNAs; RNA Interference; RNA-Binding Proteins; Receptor, Fibroblast Growth Factor, Type 2; Trans-Activators; Transforming Growth Factor beta; Biochemistry, Genetics and Molecular Biology (all)|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||26-lug-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.celrep.2016.06.055|
|Appare nelle tipologie:||01 - Articolo su periodico|