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The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer
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, loca...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280983/ https://www.ncbi.nlm.nih.gov/pubmed/32365858 http://dx.doi.org/10.3390/cancers12051122 |
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author | Friedrich, Maik Wiedemann, Karolin Reiche, Kristin Puppel, Sven-Holger Pfeifer, Gabriele Zipfel, Ivonne Binder, Stefanie Köhl, Ulrike Müller, Gerd A. Engeland, Kurt Aigner, Achim Füssel, Susanne Fröhner, Michael Peitzsch, Claudia Dubrovska, Anna Rade, Michael Christ, Sabina Schreiber, Stephan Hackermüller, Jörg Lehmann, Jörg Toma, Marieta I. Muders, Michael H. Sommer, Ulrich Baretton, Gustavo B. Wirth, Manfred Horn, Friedemann |
author_facet | Friedrich, Maik Wiedemann, Karolin Reiche, Kristin Puppel, Sven-Holger Pfeifer, Gabriele Zipfel, Ivonne Binder, Stefanie Köhl, Ulrike Müller, Gerd A. Engeland, Kurt Aigner, Achim Füssel, Susanne Fröhner, Michael Peitzsch, Claudia Dubrovska, Anna Rade, Michael Christ, Sabina Schreiber, Stephan Hackermüller, Jörg Lehmann, Jörg Toma, Marieta I. Muders, Michael H. Sommer, Ulrich Baretton, Gustavo B. Wirth, Manfred Horn, Friedemann |
author_sort | Friedrich, Maik |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7280983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72809832020-06-15 The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer Friedrich, Maik Wiedemann, Karolin Reiche, Kristin Puppel, Sven-Holger Pfeifer, Gabriele Zipfel, Ivonne Binder, Stefanie Köhl, Ulrike Müller, Gerd A. Engeland, Kurt Aigner, Achim Füssel, Susanne Fröhner, Michael Peitzsch, Claudia Dubrovska, Anna Rade, Michael Christ, Sabina Schreiber, Stephan Hackermüller, Jörg Lehmann, Jörg Toma, Marieta I. Muders, Michael H. Sommer, Ulrich Baretton, Gustavo B. Wirth, Manfred Horn, Friedemann Cancers (Basel) Article 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. MDPI 2020-04-30 /pmc/articles/PMC7280983/ /pubmed/32365858 http://dx.doi.org/10.3390/cancers12051122 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Friedrich, Maik Wiedemann, Karolin Reiche, Kristin Puppel, Sven-Holger Pfeifer, Gabriele Zipfel, Ivonne Binder, Stefanie Köhl, Ulrike Müller, Gerd A. Engeland, Kurt Aigner, Achim Füssel, Susanne Fröhner, Michael Peitzsch, Claudia Dubrovska, Anna Rade, Michael Christ, Sabina Schreiber, Stephan Hackermüller, Jörg Lehmann, Jörg Toma, Marieta I. Muders, Michael H. Sommer, Ulrich Baretton, Gustavo B. Wirth, Manfred Horn, Friedemann The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer |
title | The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer |
title_full | The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer |
title_fullStr | The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer |
title_full_unstemmed | The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer |
title_short | The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer |
title_sort | role of lncrnas tapir-1 and -2 as diagnostic markers and potential therapeutic targets in prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280983/ https://www.ncbi.nlm.nih.gov/pubmed/32365858 http://dx.doi.org/10.3390/cancers12051122 |
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