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

Autor: Friedrich M; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Wiedemann K; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Reiche K; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Puppel SH; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Pfeifer G; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany., Zipfel I; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany., Binder S; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany., Köhl U; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Müller GA; Molecular Oncology, Medical School University of Leipzig, Semmelweisstr. 14, D-04103 Leipzig, Germany.; Department of Chemistry and Biochemistry, University of California at Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA., Engeland K; Molecular Oncology, Medical School University of Leipzig, Semmelweisstr. 14, D-04103 Leipzig, Germany., Aigner A; Clinical Pharmacology, Rudolf-Boehm-Institute for Pharmacology and Toxicology, Leipzig University, Faculty of Medicine, Härtelstr. 16-18, D-04107 Leipzig, Germany., Füssel S; Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany., Fröhner M; Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.; Zeisigwaldklinik BETHANIEN, Zeisigwaldstraße 101, D-09130 Chemnitz, Germany., Peitzsch C; National Center for Tumor Diseases (NCT), Partner Site Dresden, D-01307 Germany: German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.; 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.; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany., Dubrovska A; 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.; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology-OncoRay, D-01328 Dresden, Germany., Rade M; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Christ S; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany., Schreiber S; Helmholtz Centre for Environmental Research-UFZ, Young Investigators Group Bioinformatics & Transcriptomics, Permoserstr. 15, D-04318 Leipzig, Germany., Hackermüller J; Helmholtz Centre for Environmental Research-UFZ, Young Investigators Group Bioinformatics & Transcriptomics, Permoserstr. 15, D-04318 Leipzig, Germany., Lehmann J; Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and Immunology, GLP Test Facility, Perlickstr.1, D-04103 Leipzig, Germany., Toma MI; Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany.; Institute of Pathology, Universitätsklinikum Bonn, Venusberg-Campus 1, D-53127 Bonn, Germany., Muders MH; Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany.; Rudolf-Becker-Laboratory for Prostate Cancer Research, Institute of Pathology, Universitätsklinikum Bonn, Venusberg-Campus 1, D-53127 Bonn, Germany., Sommer U; Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany., Baretton GB; Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, D-01307 Dresden, Germany., Wirth M; Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany., Horn F; Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany.; Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology, RIBOLUTION Biomarker Center Perlickstr. 1, D-04103 Leipzig, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 Apr 30; Vol. 12 (5). Date of Electronic Publication: 2020 Apr 30.
DOI: 10.3390/cancers12051122
Abstrakt: 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.
Competing Interests: We would like to disclose an application for patent protection of identified biomarkers by the following authors: K.R., S.F., S.C., M.F., J.H., M.W. and F.H.
Databáze: MEDLINE
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