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Title (Primary) The role of lncRNAs TAPIR-1 and -2 as diagnostic markers and potential therapeutic targets in prostate cancer
Author 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.;
Journal Cancers
Year 2020
Department MOLSYB;
Volume 12
Issue 5
Language englisch;
POF III (all) T42; F11;
Supplements https://www.mdpi.com/2072-6694/12/5/1122/s1
Keywords lncRNA; prostate cancer; diagnostic marker; therapeutic target; p53; cell cycle arrest; radiation resistance
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.

ID 23081
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=23081
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. (2020):
The role of lncRNAs TAPIR-1 and -2 as diagnostic markers and potential therapeutic targets in prostate cancer
Cancers 12 (5), art. 1122