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

Aditya Parikh, Christine Lee, Peronne Joseph, Sergio Marchini, Alessia Baccarini, Valentin Kolev, Chiara Romualdi, Robert Fruscio, Hardik Shah, Feng Wang, Gavriel Mullokandov, David Fishman, Maurizio D'Incalci, Jamal Rahaman, Tamara Kalir, Raymond W. Redline, Brian D. Brown, Goutham Narla, Analisa Difeo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number2977
JournalNature Communications
Volume5
DOIs
Publication statusPublished - Jan 7 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

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