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microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial–mesenchymal transition

Author

Listed:
  • Aditya Parikh

    (Mount Sinai School of Medicine
    Mount Sinai School of Medicine)

  • Christine Lee

    (Mount Sinai School of Medicine
    Case Comprehensive Cancer Center, Case Western Reserve University)

  • Peronne Joseph

    (Case Comprehensive Cancer Center, Case Western Reserve University)

  • Sergio Marchini

    (IRCCS-Istituto di Ricerche Farmacologiche ‘Mario Negri’, via La Masa 19, 20156 Milano, Italy)

  • Alessia Baccarini

    (Mount Sinai School of Medicine)

  • Valentin Kolev

    (The Mount Sinai School of Medicine)

  • Chiara Romualdi

    (Universtia' degli studi di Padova, Via U.Bassi 58/B)

  • Robert Fruscio

    (Clinic of Obstetrics and Gynecology, University of Milano-Bicocca, San Gerardo Hospital
    MaNGO Group)

  • Hardik Shah

    (Mount Sinai School of Medicine)

  • Feng Wang

    (The Mount Sinai School of Medicine)

  • Gavriel Mullokandov

    (Mount Sinai School of Medicine)

  • David Fishman

    (The Mount Sinai School of Medicine)

  • Maurizio D’Incalci

    (IRCCS-Istituto di Ricerche Farmacologiche ‘Mario Negri’, via La Masa 19, 20156 Milano, Italy)

  • Jamal Rahaman

    (The Mount Sinai School of Medicine)

  • Tamara Kalir

    (MaNGO Group
    Mount Sinai School of Medicine)

  • Raymond W. Redline

    (University Hospitals Case Medical Center)

  • Brian D. Brown

    (Mount Sinai School of Medicine)

  • Goutham Narla

    (Mount Sinai School of Medicine
    Mount Sinai School of Medicine
    Case Comprehensive Cancer Center, Case Western Reserve University
    Institute for Transformative Molecular Medicine, 2103 Cornell Road, Cleveland, Ohio 44106, USA)

  • Analisa DiFeo

    (Mount Sinai School of Medicine
    Case Comprehensive Cancer Center, Case Western Reserve University)

Abstract

Ovarian cancer is a leading cause of cancer deaths among women. Effective targets to treat advanced epithelial ovarian cancer (EOC) and biomarkers to predict treatment response are still lacking because of the complexity of pathways involved in ovarian cancer progression. Here we show that miR-181a promotes TGF-β-mediated epithelial-to-mesenchymal transition via repression of its functional target, Smad7. miR-181a and phosphorylated Smad2 are enriched in recurrent compared with matched-primary ovarian tumours and their expression is associated with shorter time to recurrence and poor outcome in patients with EOC. Furthermore, ectopic expression of miR-181a results in increased cellular survival, migration, invasion, drug resistance and in vivo tumour burden and dissemination. In contrast, miR-181a inhibition via decoy vector suppression and Smad7 re-expression results in significant reversion of these phenotypes. Combined, our findings highlight an unappreciated role for miR-181a, Smad7, and the TGF-β signalling pathway in high-grade serous ovarian cancer.

Suggested Citation

  • Aditya Parikh & Christine Lee & Peronne Joseph & Sergio Marchini & Alessia Baccarini & Valentin Kolev & Chiara Romualdi & Robert Fruscio & Hardik Shah & Feng Wang & Gavriel Mullokandov & David Fishman, 2014. "microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial–mesenchymal transition," Nature Communications, Nature, vol. 5(1), pages 1-16, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms3977
    DOI: 10.1038/ncomms3977
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