A comprehensive repertoire of tRNA-derived fragments in prostate cancer.

// Michael Olvedy 1, 4, 5, * , Mauro Scaravilli 2, 3, * , Youri Hoogstrate 1 , Tapio Visakorpi 2, 3, # , Guido Jenster 1, # , Elena S. Martens-Uzunova 1, # 1 Department of Urology, Erasmus MC, Rotterdam, The Netherlands 2 Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland 3 Fimlab Laboratories, Tampere University Hospital, Tampere, Finland 4 Current address: VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium 5 Current address: Center for Human Genetics, KULeuven, Leuven, Belgium * These authors contributed equally to this work # Three last authors contributed equally to this work Correspondence to: Elena S. Martens-Uzunova, e-mail: e.martens@erasmusmc.nl Keywords: tRNA-derived fragments (tRFs), prostate cancer (PCa), RNA-sequencing, non-coding RNA, biomarker Received: September 04, 2015      Accepted: March 02, 2016      Published: March 23, 2016 ABSTRACT Prostate cancer (PCa) is the most common cancer among men in developed countries. Although its genetic background is thoroughly investigated, rather little is known about the role of small non-coding RNAs (sncRNA) in this disease. tRNA-derived fragments (tRFs) represent a new class of sncRNAs, which are present in a broad range of species and have been reported to play a role in several cellular processes. Here, we analyzed the expression of tRFs in fresh frozen patient samples derived from normal adjacent prostate and different stages of PCa by RNA-sequencing. We identified 598 unique tRFs, many of which are deregulated in cancer samples when compared to normal adjacent tissue. Most of the identified tRFs are derived from the 5’- and 3’-ends of mature cytosolic tRNAs, but we also found tRFs produced from other parts of tRNAs, including pre-tRNA trailers and leaders, as well as tRFs from mitochondrial tRNAs. The 5’-derived tRFs comprise the most abundant class of tRFs in general and represent the major class among upregulated tRFs. The 3’-derived tRFs types are dominant among downregulated tRFs in PCa. We validated the expression of three tRFs using qPCR. The ratio of tRFs derived from tRNA LysCTT and tRNA PheGAA emerged as a good indicator of progression-free survival and a candidate prognostic marker. This study provides a systematic catalogue of tRFs and their dysregulation in PCa and can serve as the basis for further research on the biomarker potential and functional roles of tRFs in this disease.