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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84693 |
| Date | 13 April 2023 |
| Creators | 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 |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2072-6694, 1122 |
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