Abstract B47: microRNA-181a plays a critical role in ovarian cancer progression through the regulation of epithelial-mesenchymal transition

Abstract

Abstract Ovarian cancer is the most lethal gynecological cancer primarily due to advanced stage of disease at diagnosis. Effective therapeutic targets and prognostic biomarkers are still lacking due to insufficient knowledge of the pathways that regulate ovarian cancer progression. Here, we identify miR-181a as a mediator of disease dissemination through the induction of EMT and direct activation of the TGF-β signaling pathway via repression of its functional target, Smad7. High expression of miR-181a and phospho-Smad2 were associated with poor patient outcome and were enriched in recurrent compared to matched-primary tumors. Ectopic expression of miR-181a resulted in increased cellular survival, migration, drug resistance, and in vivo tumor burden, and dissemination. Conversely, targeting this miRNA using a decoy vector resulted in significant decreases in cell survival, migration, and MET in ovarian cancer cell lines. Combined, our findings identify miR-181a as a novel modulator of ovarian cancer dissemination through the induction of EMT and highlight its role as a potential biomarker and therapeutic target for aggressive late-stage ovarian cancer. Citation Format: Aditya Parikh, Christine Lee, Peronne Joseph, Sergio Marchini, Alessia Baccarini, Valentin Kolev, Chiara Romualdi, Robert Fruscio, Hardik Shah, Wang Feng, Gavriel Mullokandov, David Fishman, Maurizio D'Incalci, Jamal Rahaman, Tamara Kalir, Raymond Redline, Brian D. Brown, Goutham Narla, Analisa DiFeo. microRNA-181a plays a critical role in ovarian cancer progression through the regulation of epithelial-mesenchymal transition. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B47.