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 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.
Highlights
Prostate cancer (PCa) is the second most common cancer in men worldwide [1]
Its genetic background is thoroughly investigated, rather little is known about the role of small non-coding RNAs in this disease. tRNAderived fragments 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
The rapid progress and popularity of high throughput sequencing led to the discovery of a novel class of sncRNAs derived from tRNAs and named tRNAderived fragments [3,4,5]. tRFs are present across all domains of life [6,7,8]
Summary
The treatment of PCa is hampered by the lack of reliable markers for disease outcome prediction leading to incorrect patient stratification, overtreatment and consequent side effects from prostatectomy and radiation therapy [2]. A better understanding of the molecular mechanisms behind the onset and progression of PCa is needed in order to discover better markers and develop new therapeutic strategies. The role of small non-coding RNAs (sncRNAs) other than microRNAs (miRNAs) in PCa is poorly understood. The rapid progress and popularity of high throughput sequencing led to the discovery of a novel class of sncRNAs derived from tRNAs and named tRNAderived fragments (tRFs) [3,4,5]. While initially considered random products of tRNA turnover, their abundance and ubiquitous expression suggest that tRFs are actual biological entities [6, 7]
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