Cancers (Apr 2020)
The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer
- Maik Friedrich,
- Karolin Wiedemann,
- Kristin Reiche,
- Sven-Holger Puppel,
- Gabriele Pfeifer,
- Ivonne Zipfel,
- Stefanie Binder,
- Ulrike Köhl,
- Gerd A. Müller,
- Kurt Engeland,
- Achim Aigner,
- Susanne Füssel,
- Michael Fröhner,
- Claudia Peitzsch,
- Anna Dubrovska,
- Michael Rade,
- Sabina Christ,
- Stephan Schreiber,
- Jörg Hackermüller,
- Jörg Lehmann,
- Marieta I. Toma,
- Michael H. Muders,
- Ulrich Sommer,
- Gustavo B. Baretton,
- Manfred Wirth,
- Friedemann Horn
Affiliations
- Maik Friedrich
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Karolin Wiedemann
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Kristin Reiche
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Sven-Holger Puppel
- Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany
- Gabriele Pfeifer
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Ivonne Zipfel
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Stefanie Binder
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Ulrike Köhl
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- Gerd A. Müller
- Molecular Oncology, Medical School University of Leipzig, Semmelweisstr. 14, D-04103 Leipzig, Germany
- Kurt Engeland
- Molecular Oncology, Medical School University of Leipzig, Semmelweisstr. 14, D-04103 Leipzig, Germany
- Achim Aigner
- Clinical Pharmacology, Rudolf-Boehm-Institute for Pharmacology and Toxicology, Faculty of Medicine, Leipzig University, Härtelstr. 16–18, D-04107 Leipzig, Germany
- Susanne Füssel
- Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany
- Michael Fröhner
- Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany
- Claudia Peitzsch
- National Center for Tumor Diseases (NCT), Partner Site Dresden, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
- Anna Dubrovska
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, D-01307 Dresden, Germany
- Michael Rade
- Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany
- Sabina Christ
- Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany
- Stephan Schreiber
- Helmholtz Centre for Environmental Research—UFZ, Young Investigators Group Bioinformatics & Transcriptomics, Permoserstr. 15, D-04318 Leipzig, Germany
- Jörg Hackermüller
- Helmholtz Centre for Environmental Research—UFZ, Young Investigators Group Bioinformatics & Transcriptomics, Permoserstr. 15, D-04318 Leipzig, Germany
- Jörg Lehmann
- Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and Immunology, GLP Test Facility, Perlickstr. 1, D-04103 Leipzig, Germany
- Marieta I. Toma
- Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany
- Michael H. Muders
- Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany
- Ulrich Sommer
- Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany
- Gustavo B. Baretton
- Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany
- Manfred Wirth
- Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany
- Friedemann Horn
- Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
- DOI
- https://doi.org/10.3390/cancers12051122
- Journal volume & issue
-
Vol. 12,
no. 5
p. 1122
Abstract
In search of new biomarkers suitable for the diagnosis and treatment of prostate cancer, genome-wide transcriptome sequencing was carried out with tissue specimens from 40 prostate cancer (PCa) and 8 benign prostate hyperplasia patients. We identified two intergenic long non-coding transcripts, located in close genomic proximity, which are highly expressed in PCa. Microarray studies on a larger cohort comprising 155 patients showed a profound diagnostic potential of these transcripts (AUC~0.94), which we designated as tumor associated prostate cancer increased lncRNA (TAPIR-1 and -2). To test their therapeutic potential, knockdown experiments with siRNA were carried out. The knockdown caused an increase in the p53/TP53 tumor suppressor protein level followed by downregulation of a large number of cell cycle- and DNA-damage repair key regulators. Furthermore, in radiation therapy resistant tumor cells, the knockdown leads to a renewed sensitization of these cells to radiation treatment. Accordingly, in a preclinical PCa xenograft model in mice, the systemic application of nanoparticles loaded with siRNA targeting TAPIR-1 significantly reduced tumor growth. These findings point to a crucial role of TAPIR-1 and -2 in PCa.
Keywords