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 tRNALysCTT and tRNAPheGAA 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.

Over the recent years, Next Generation Sequencing (NGS) technologies targeting the microRNA transcriptome revealed the existence of many different RNA fragments derived from small RNA species other than microRNA. Although initially discarded as RNA turnover artifacts, accumulating evidence suggests that RNA fragments derived from small nucleolar RNA (snoRNA) and transfer RNA (tRNA) are not just random degradation products but rather stable entities, which may have functional activity in the normal and malignant cell. This review summarizes new findings describing the detection and alterations in expression of snoRNA-derived (sdRNA) and tRNA-derived (tRF) RNAs. We focus on the possible interactions of sdRNAs and tRFs with the canonical microRNA pathways in the cell and present current hypotheses on the function of these RNAs.