miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-β-Induced Epithelial-to-Mesenchymal Transition

Margherita Puppo, Gabriele Bucci, Martina Rossi, Matteo Giovarelli, Domenico Bordo, Arfa Moshiri, Franco Gorlero, Roberto Gherzi, Paola Briata

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)967-978
Number of pages12
JournalCell Reports
Volume16
Issue number4
DOIs
Publication statusPublished - Jul 26 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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