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Article

The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer

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Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
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Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany
3
Molecular Oncology, Medical School University of Leipzig, Semmelweisstr. 14, D-04103 Leipzig, Germany
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Department of Chemistry and Biochemistry, University of California at Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA
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Clinical Pharmacology, Rudolf-Boehm-Institute for Pharmacology and Toxicology, Faculty of Medicine, Leipzig University, Härtelstr. 16–18, D-04107 Leipzig, Germany
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Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany
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Zeisigwaldklinik BETHANIEN, Zeisigwaldstraße 101, D-09130 Chemnitz, Germany
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National Center for Tumor Diseases (NCT), Partner Site Dresden, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
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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
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German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
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Helmholtz-Zentrum Dresden—Rossendorf, Institute of Radiooncology—OncoRay, D-01328 Dresden, Germany
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Helmholtz Centre for Environmental Research—UFZ, Young Investigators Group Bioinformatics & Transcriptomics, Permoserstr. 15, D-04318 Leipzig, Germany
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Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and Immunology, GLP Test Facility, Perlickstr. 1, D-04103 Leipzig, Germany
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Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany
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Institute of Pathology, Universitätsklinikum Bonn, Venusberg-Campus 1, D-53127 Bonn, Germany
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Rudolf-Becker-Laboratory for Prostate Cancer Research, Institute of Pathology, Universitätsklinikum Bonn, Venusberg-Campus 1, D-53127 Bonn, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1122; https://doi.org/10.3390/cancers12051122
Received: 23 February 2020 / Revised: 13 April 2020 / Accepted: 21 April 2020 / Published: 30 April 2020
(This article belongs to the Special Issue Cancer Biomarkers)
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. View Full-Text
Keywords: lncRNA; prostate cancer; diagnostic marker; therapeutic target; p53; cell cycle arrest; radiation resistance lncRNA; prostate cancer; diagnostic marker; therapeutic target; p53; cell cycle arrest; radiation resistance
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Figure 1

MDPI and ACS Style

Friedrich, M.; Wiedemann, K.; Reiche, K.; Puppel, S.-H.; Pfeifer, G.; Zipfel, I.; Binder, S.; Köhl, U.; Müller, G.A.; Engeland, K.; Aigner, A.; Füssel, S.; Fröhner, M.; Peitzsch, C.; Dubrovska, A.; Rade, M.; Christ, S.; Schreiber, S.; Hackermüller, J.; Lehmann, J.; Toma, M.I.; Muders, M.H.; Sommer, U.; Baretton, G.B.; Wirth, M.; Horn, F. The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer. Cancers 2020, 12, 1122. https://doi.org/10.3390/cancers12051122

AMA Style

Friedrich M, Wiedemann K, Reiche K, Puppel S-H, Pfeifer G, Zipfel I, Binder S, Köhl U, Müller GA, Engeland K, Aigner A, Füssel S, Fröhner M, Peitzsch C, Dubrovska A, Rade M, Christ S, Schreiber S, Hackermüller J, Lehmann J, Toma MI, Muders MH, Sommer U, Baretton GB, Wirth M, Horn F. The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer. Cancers. 2020; 12(5):1122. https://doi.org/10.3390/cancers12051122

Chicago/Turabian Style

Friedrich, Maik, 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, and Friedemann Horn. 2020. "The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer" Cancers 12, no. 5: 1122. https://doi.org/10.3390/cancers12051122

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