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 Î² (TGF-Î²)-induced EMT in mammary gland cells. Sustained KHSRP expression limits TGF-Î²-dependent induction of EMT factors and cell migration, whereas its knockdown in untreated cells mimics TGF-Î²-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-Î²-induced KHSRP silencing is central in a pathway leading to gene-expression changes that contribute to the cellular changes linked to EMT.
|Titolo:||miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-Î²-Induced Epithelial-to-Mesenchymal Transition|
|Data di pubblicazione:||2016|
|Appare nelle tipologie:||01.01 - Articolo su rivista|
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|miRNA mediated silencing KHSRP_2016.pdf||miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-β-Induced Epithelial-to-Mesenchymal Transition Puppo, Margherita; Bucci, Gabriele; Rossi, Martina; Giovarelli, Matteo; Bordo, Domenico; Moshiri, Arfa; Gorlero, Franco; Gherzi, Roberto; Briata, Paola ISSN: 22111247 , 2211-1247; DOI: 10.1016/j.celrep.2016.06.055 Cell reports. , 2016, Vol.16(4), p.967-978. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.For commercial reuse, permission must be requested to Elsevier||Versione editoriale||Open Access Visualizza/Apri|