Ago-RIP-Seq identifies Polycomb repressive complex I member CBX7 as a major target of miR-375 in prostate cancer progression
| Autor: | Vladimir Kuryshev, Boris Hadaschik, Michael Falkenstein, Diana Tichy, Doreen Heckmann, Yanis Tolstov, Julia Schüler, Stefan Duensing, Wilfried Roth, Agnes Hotz-Wagenblatt, Holger Sültmann, Julia M. A. Pickl, Markus Hohenfellner, Glen Kristiansen, Daniel Reidenbach |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Pathology Tumor suppressor gene Transplantation Heterologous Mice Nude Disease miR-375 03 medical and health sciences Prostate cancer Mir-375 Cell Line Tumor Internal medicine Biomarkers Tumor medicine Animals Humans Tumor growth Epigenetics Polycomb Repressive Complex 1 business.industry Gene Expression Profiling Prostatic Neoplasms Cancer prostate cancer medicine.disease University hospital Gene Expression Regulation Neoplastic MicroRNAs Gene Ontology 030104 developmental biology CBX7 Disease Progression biomarker business Ago-RIP-Seq Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Julia M.A. Pickl 1 , Diana Tichy 2 , Vladimir Y. Kuryshev 1 , Yanis Tolstov 3 , Michael Falkenstein 3 , Julia Schuler 4 , Daniel Reidenbach 1 , Agnes Hotz-Wagenblatt 5 , Glen Kristiansen 6 , Wilfried Roth 7 , Boris Hadaschik 8 , Markus Hohenfellner 8 , Stefan Duensing 3 , Doreen Heckmann 1 , Holger Sultmann 1 1 Cancer Genome Research Group, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany 2 Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany 3 Section of Molecular Urooncology, Department of Urology, University of Heidelberg School of Medicine, Heidelberg, Germany 4 Oncotest GmbH, Institute for Experimental Oncology, Freiburg, Germany 5 Bioinformatics Group, Core Facility Genomics & Proteomics, German Cancer Research Center (DKFZ), Heidelberg, Germany 6 Institute of Pathology, Center for Integrated Oncology, University of Bonn, Bonn, Germany 7 NCT Tissue Bank of The National Center of Tumor Diseases (NCT) and Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany 8 Department of Urology, University Hospital Heidelberg, Heidelberg, Germany Correspondence to: Holger Sultmann, email: h.sueltmann@dkfz.de Keywords: miR-375 , CBX7 , biomarker, prostate cancer, Ago-RIP-Seq Received: February 08, 2016 Accepted: July 09, 2016 Published: July 20, 2016 ABSTRACT Prostate cancer is a heterogeneous disease. MiR-375 is a marker for prostate cancer progression, but its cellular function is not characterized. Here, we provide the first comprehensive investigation of miR-375 in prostate cancer. We show that miR-375 is enriched in prostate cancer compared to normal cells. Furthermore, miR-375 enhanced proliferation, migration and invasion in vitro and induced tumor growth and reduced survival in vivo showing that miR-375 has oncogenic properties in prostate cancer. On the molecular level, we provide the targetome and genome-wide transcriptional changes of miR-375 expression by applying a generalized linear model for Ago-RIP-Seq and RNA-Seq, and show that miR-375 is involved in tumorigenic networks and Polycomb regulation. Integration of tissue and gene ontology data prioritized miR-375 targets and identified the tumor suppressor gene CBX7 , a member of Polycomb repressive complex 1, as a major miR-375 target. MiR-375 -mediated repression of CBX7 was accompanied by increased expression of its homolog CBX8 and activated transcriptional programs linked to malignant progression in prostate cancer cells. Tissue analysis showed association of CBX7 loss with advanced prostate cancer. Our study indicates that miR-375 exerts its tumor-promoting role in prostate cancer by influencing the epigenetic regulation of transcriptional programs through its ability to directly target the Polycomb complex member CBX7 . |
| Databáze: | OpenAIRE |
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