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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; Koehl, 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 P.; Horn, Friedemann

Fulltext ()

Cancers 12 (2020), No.5, Art. 1122, 27 pp.
ISSN: 2072-6694
Journal Article, Electronic Publication
Fraunhofer IZI ()
cell cycle arrest; diagnostic marker; lncRNA; P53; Prostate Cancer; radiation resistance; therapeutic target

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.