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

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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

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Epithelial-Mesenchymal Transition
Transforming Growth Factors
MicroRNAs
RNA Precursors
Ribonucleoproteins
Cell Movement
RNA-Binding Proteins
Cell adhesion
Alternative Splicing
Gene expression
Exons
Genes
Cells
Human Mammary Glands
Cell Adhesion
Genome
Gene Expression
Proteins
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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.

In: Cell Reports, Vol. 16, No. 4, 26.07.2016, p. 967-978.

Research output: Contribution to journalArticle

Puppo, Margherita ; Bucci, Gabriele ; Rossi, Martina ; Giovarelli, Matteo ; Bordo, Domenico ; Moshiri, Arfa ; Gorlero, Franco ; Gherzi, Roberto ; Briata, Paola. / miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-β-Induced Epithelial-to-Mesenchymal Transition. In: Cell Reports. 2016 ; Vol. 16, No. 4. pp. 967-978.
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