MP68-06 MIR-1227 ALTERS EXTRACELLULAR VESICLE SHEDDING IN PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (MP68)1 Apr 2019MP68-06 MIR-1227 ALTERS EXTRACELLULAR VESICLE SHEDDING IN PROSTATE CANCER Andrew Chin*, Valentina R. Minciacchi, Tatyana Vagner, Javier Mariscal, Minhyung Kim, Cristiana Spinelli, Mariana Sobreiro, Mandana Zandian, Sungyong You, Shivani Sharma, Nadia Zaffaroni, Paolo Gandellini, and Dolores Di Vizio Andrew Chin*Andrew Chin* More articles by this author , Valentina R. MinciacchiValentina R. Minciacchi More articles by this author , Tatyana VagnerTatyana Vagner More articles by this author , Javier MariscalJavier Mariscal More articles by this author , Minhyung KimMinhyung Kim More articles by this author , Cristiana SpinelliCristiana Spinelli More articles by this author , Mariana SobreiroMariana Sobreiro More articles by this author , Mandana ZandianMandana Zandian More articles by this author , Sungyong YouSungyong You More articles by this author , Shivani SharmaShivani Sharma More articles by this author , Nadia ZaffaroniNadia Zaffaroni More articles by this author , Paolo GandelliniPaolo Gandellini More articles by this author , and Dolores Di VizioDolores Di Vizio More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557021.56588.e8AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Extracellular vesicles (EV) play a key role in cancer development and metastasis by influencing the behavior of the primary tumor and by aiding the establishment of a pre-metastatic niche in distant organs. This process is due to the EV-mediated functional transfer of biologically active molecules including microRNA (miRNA). miR-1227 is a poorly characterized miRNA that is enriched in prostate cancer EV secreted by prostate cancer cells in comparison to non-tumorigenic prostate epithelial cells. However, the role of miR-1227 in cancer is poorly understood. Our objective is to identify the role of miR-1227 in prostate cancer. METHODS: RNA sequencing from miR-1227 stably expressing prostate cancer cells, RISCTRAP immunoprecipitation of miR-1227 bound mRNA, and 5 different in silico miRNA target prediction methods were used to identify putative miR-1227 targets. Exosomes and large oncosomes (LO) were isolated by differential ultracentrifugation followed by density gradient purification. Atomic force microscopy was used to quantify exosomes and LO secreted by prostate cancer cells stably expressing miR-1227 or vector control. RESULTS: A comparative analysis between different EV subtypes indicates that miR-1227 is enriched in LO, a class of EV that are secreted by highly invasive amoeboid-migrating cells. LO carry more RNA than the more widely studied exosomes indicating that LO may be a more robust source of EV-encapsulated miRNA. Gene ontology analysis from miR-1227 targets identified by 3 independent methods highlighted several genes related to EV secretion. miR-1227 alters the localization of several exosome and LO markers in multiple cancer cell lines, and induce the shedding of large vesicles while inhibiting the shedding of smaller exosome sized vesicles. Furthermore, miR-1227 induces the migration of poorly migratory cancer cells and increases the expression of tumor supportive cytokines. CONCLUSIONS: Together these data hint that miR-1227 may promote prostate cancer progression through several mechanisms including alteration of EV shedding. Source of Funding: 2018-2020 Chesapeake Urology Associates Sanford J. Siegel, MD Prostate Cancer Research Scholar Award; 2018-2020 Luke Wu-Jei Chang Discovery Fund; 2017-2022 R01CA218526; 2016-2019 PI DoD PCRP Award PC150836. West Hollywood, CA; Los Angeles, CA; Milan, Italy; West Hollywood, CA© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e977-e977 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Chin* More articles by this author Valentina R. Minciacchi More articles by this author Tatyana Vagner More articles by this author Javier Mariscal More articles by this author Minhyung Kim More articles by this author Cristiana Spinelli More articles by this author Mariana Sobreiro More articles by this author Mandana Zandian More articles by this author Sungyong You More articles by this author Shivani Sharma More articles by this author Nadia Zaffaroni More articles by this author Paolo Gandellini More articles by this author Dolores Di Vizio More articles by this author Expand All Advertisement PDF downloadLoading ...