Abstract
Abstract MicroRNAs (miRNAs) in solid malignancies can behave as predictors of either good or poor outcome. This is the case with members of the miR-200 family, which are the primary regulators of the epithelial to mesenchymal transition and have been reported to act as both oncogenes and tumor suppressors in independent studies. Expression of miR-200c was assessed in a panel of ovarian cancer cell lines with inherent or acquired drug-resistance. Luciferase reporter assay and ribonucleic-immuno-precipitation assay was used to in vitro characterise the complexes between miR-200c, HuR and class III β-tubulin (TUBB3). Nanofluidic technology and immunohistochemistry were used to analyze the expression of HuR, TUBB3 and miR-200c in 220 ovarian cancer patients. Using such approach, we demonstrated that overexpression of miR-200c in ovarian cancer resulted in poor or good outcome depending on interaction with the RNA binding protein HuR. When the localization of HuR was confined in the nucleus, high expression of miR-200c suppressed class III β-tubulin (TUBB3) expression and resulted in a good prognosis, whereas when HuR occurred in cytoplasm, the same miRNA enhanced TUBB3 expression and produced a poor outcome. Indeed, in an ovarian cancer cell line model, the miR-200c increased HuR binding on TUBB3 mRNA in stressing microenvironmental conditions. This study demonstrated how the prognostic power of a single factor can depend on interactions with additional factors. Through a multidimensional analysis of all components, the actual mechanism(s) underlying the aggressive biological behavior of ovarian cancer can be unraveled, and the prognosis of ovarian cancer patients can be rendered based on rational explanations. Citation Format: Silvia Prislei, Enrica Martinelli, Marisa Mariani, Giuseppina Raspaglio, Steven Sieber, Gabriella Ferrandina, Shohreh Shahabi, Giovanni Scambia, Cristiano Ferlini. MiR-200c can mediate either poor or good outcome in ovarian cancer depending on HuR localization in the cell. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1957. doi:10.1158/1538-7445.AM2013-1957
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