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A comprehensive repertoire of tRNA-derived fragments in prostate cancer.
Oncotarget 2016; 7(17):24766-77O

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.

Authors+Show Affiliations

Department of Urology, Erasmus MC, Rotterdam, The Netherlands. Current address: VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium. Current address: Center for Human Genetics, KU Leuven, Leuven, Belgium.Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.Department of Urology, Erasmus MC, Rotterdam, The Netherlands.Institute of Biosciences and Medical Technology-BioMediTech, University of Tampere, Tampere, Finland. Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.Department of Urology, Erasmus MC, Rotterdam, The Netherlands.Department of Urology, Erasmus MC, Rotterdam, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27015120

Citation

Olvedy, Michael, et al. "A Comprehensive Repertoire of tRNA-derived Fragments in Prostate Cancer." Oncotarget, vol. 7, no. 17, 2016, pp. 24766-77.
Olvedy M, Scaravilli M, Hoogstrate Y, et al. A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget. 2016;7(17):24766-77.
Olvedy, M., Scaravilli, M., Hoogstrate, Y., Visakorpi, T., Jenster, G., & Martens-Uzunova, E. S. (2016). A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget, 7(17), pp. 24766-77. doi:10.18632/oncotarget.8293.
Olvedy M, et al. A Comprehensive Repertoire of tRNA-derived Fragments in Prostate Cancer. Oncotarget. 2016 Apr 26;7(17):24766-77. PubMed PMID: 27015120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comprehensive repertoire of tRNA-derived fragments in prostate cancer. AU - Olvedy,Michael, AU - Scaravilli,Mauro, AU - Hoogstrate,Youri, AU - Visakorpi,Tapio, AU - Jenster,Guido, AU - Martens-Uzunova,Elena S, PY - 2015/09/04/received PY - 2016/03/02/accepted PY - 2016/3/26/entrez PY - 2016/3/26/pubmed PY - 2017/12/28/medline KW - RNA-sequencing KW - biomarker KW - non-coding RNA KW - prostate cancer (PCa) KW - tRNA-derived fragments (tRFs) SP - 24766 EP - 77 JF - Oncotarget JO - Oncotarget VL - 7 IS - 17 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27015120/A_comprehensive_repertoire_of_tRNA_derived_fragments_in_prostate_cancer_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=8293 DB - PRIME DP - Unbound Medicine ER -