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

• Main Authors: Maik Friedrich, Karolin Wiedemann, Kristin Reiche, Sven-Holger Puppel, Gabriele Pfeifer, Ivonne Zipfel, Stefanie Binder, Ulrike Köhl, Gerd A. Müller, Kurt Engeland, Achim Aigner, Susanne Füssel, Michael Fröhner, Claudia Peitzsch, Anna Dubrovska, Michael Rade, Sabina Christ, Stephan Schreiber, Jörg Hackermüller, Jörg Lehmann, Marieta I. Toma, Michael H. Muders, Ulrich Sommer, Gustavo B. Baretton, Manfred Wirth, Friedemann Horn
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Cancers
• Subjects: lncRNA; prostate cancer; diagnostic marker; therapeutic target; p53; cell cycle arrest
• Online Access: https://www.mdpi.com/2072-6694/12/5/1122

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 (<i>TAPIR-1</i> and <i>-2</i><i>)</i>. 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 <i>DNA</i>-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 <i>TAPIR-1</i> significantly reduced tumor growth. These findings point to a crucial role of <i>TAPIR-1 </i>and <i>-2</i> in PCa.