Prostate cancer (PCa) is the most common cancer among men in developed countries. Although its genetic background is thoroughly investigated, rather littleis 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 ina 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 ingeneral and represent the major class among upregulated tRFs. The 3'-derived tRFs types are dominant among downregulated tRFs in PCa. We validated the expressionof three tRFs using qPCR. The ratio of tRFs derived from tRNALys CTT 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.

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Department of Urology

Olvedy, M., Scaravilli, M., Hoogstrate, Y., Visakorpi, T., Jenster, G., & Martens-Uzunova, E. (2016). A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget, 7(17), 24766–24777. doi:10.18632/oncotarget.8293