Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer
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Felix Royo1,2,*, Patricia Zuñiga-Garcia1,*, Verónica Torrano1,*, Ana Loizaga3,*, Pilar Sanchez-Mosquera1, Aitziber Ugalde-Olano4, Esperanza González1, Ana R. Cortazar1, Laura Palomo1, Sonia Fernández-Ruiz1, Isabel Lacasa-Viscasillas3, Maria Berdasco5, James D. Sutherland1, Rosa Barrio1, Amaia Zabala-Letona1, Natalia Martín-Martín1, Amaia Arruabarrena-Aristorena1, Lorea Valcarcel-Jimenez1, Alfredo Caro-Maldonado1, Jorge Gonzalez-Tampan3, Guido Cachi-Fuentes3, Manel Esteller5, Ana M. Aransay1,2, Miguel Unda3, Juan M. Falcón-Pérez1,2,6,Ω, Arkaitz Carracedo1,6,7,Ω
1CIC bioGUNE, Bizkaia Technology Park, Biscay, Spain
2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain
3Department of Urology, Basurto University Hospital, Bilbao, Spain
4Department of Pathology, Basurto University Hospital, Bilbao, Spain
5Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
6Ikerbasque, Basque Foundation for Science, Bizkaia, Spain
7Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), Bizkaia, Spain
*These authors contributed equally to this work
ΩThese authors contributed equally to this work
Arkaitz Carracedo, e-mail: [email protected]
Juan M. Falcón-Pérez, e-mail: [email protected]
Keywords: extracellular vesicles, exosomes, prostate cancer, urine biomakers
Received: August 18, 2015 Accepted: November 26, 2015 Published: January 12, 2016
Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa.
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