<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Panoutsopoulou, K.</style></author><author><style face="normal" font="default" size="100%">Magkou, P.</style></author><author><style face="normal" font="default" size="100%">Dreyer, T.</style></author><author><style face="normal" font="default" size="100%">Dorn, J.</style></author><author><style face="normal" font="default" size="100%">Obermayr, E.</style></author><author><style face="normal" font="default" size="100%">Mahner, S.</style></author><author><style face="normal" font="default" size="100%">van Gorp, T.</style></author><author><style face="normal" font="default" size="100%">Braicu, I.</style></author><author><style face="normal" font="default" size="100%">Magdolen, V.</style></author><author><style face="normal" font="default" size="100%">Zeillinger, R.</style></author><author><style face="normal" font="default" size="100%">Avgeris, M.</style></author><author><style face="normal" font="default" size="100%">Scorilas, A.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">tRNA-derived small RNA 3'U-tRF(ValCAC) promotes tumour migration and early progression in ovarian cancer</style></title><secondary-title><style face="normal" font="default" size="100%">European Journal of Cancer</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">*Ovarian Neoplasms/genetics</style></keyword><keyword><style  face="normal" font="default" size="100%">*Rna</style></keyword><keyword><style  face="normal" font="default" size="100%">3'U-tRF</style></keyword><keyword><style  face="normal" font="default" size="100%">apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">competing financial interests or personal relationships that could have appeared</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular diagnostics</style></keyword><keyword><style  face="normal" font="default" size="100%">ncRNAs</style></keyword><keyword><style  face="normal" font="default" size="100%">non-coding RNAs</style></keyword><keyword><style  face="normal" font="default" size="100%">Prognosis</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Transfer/genetics/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">to influence the work reported in this paper.</style></keyword><keyword><style  face="normal" font="default" size="100%">tRF-1</style></keyword><keyword><style  face="normal" font="default" size="100%">tRFs</style></keyword><keyword><style  face="normal" font="default" size="100%">tRNA-derived fragments</style></keyword><keyword><style  face="normal" font="default" size="100%">tsRNAs</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">180</style></volume><pages><style face="normal" font="default" size="100%">134-145</style></pages><isbn><style face="normal" font="default" size="100%">1879-0852 (Electronic)0959-8049 (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">INTRODUCTION: Despite recent advances in epithelial ovarian cancer (EOC) management, the highly heterogenous histological/molecular tumour background and patients' treatment response obstructs personalised prognosis and therapeutics. Herein, we have studied the role and clinical utility of the novel subclass of tRNA-derived small RNA fragments emerging via 3'-trailer processing of pre-tRNAs (3'U-tRFs) in EOC. METHODS: SK-OV-3 and OVCAR-3 cells were used for in vitro study. Following transfection, cell growth and migration were assessed by CCK8 and wound healing assays, respectively. 3'U-tRFs levels were assessed by reverse transcription quantitative PCR (RT-qPCR), following 3'-end RNA polyadenylation. A screening (OVCAD, n = 100) and institutionally independent validation (TU Munich, n = 103) cohorts were employed for survival analysis using disease progression and patients' death as clinical end-points. Bootstrap analysis was performed for internal validation, and decision curve analysis was used to evaluate clinical benefit on disease prognosis. RESULTS: Following primary clinical assessment, target prediction and gene ontology analyses, the 3'U-tRF(ValCAC) (derived from pre-tRNA(ValCAC)) was highlighted to regulate cell proliferation and adhesion, and to correlate with inferior patients' outcome. 3'U-tRF(ValCAC) transfection of SK-OV-3 and OVCAR-3 cells resulted in significantly increased cell growth and migration, in a dose-dependent manner. Elevated tumour 3'U-tRF(ValCAC) levels were associated with significantly higher risk for early progression and worse survival following first-line platinum-based chemotherapy, independently of patients' clinicopathological data, chemotherapy response, and residual tumour. Interestingly, 3'U-tRF(ValCAC)-fitted multivariate models improved risk stratification and provided superior clinical net benefit in prediction of treatment outcome compared to disease established markers. CONCLUSIONS: 3'U-tRF(ValCAC) promotes tumour cell growth and migration and supports modern risk stratification and prognosis in EOC.</style></abstract><accession-num><style face="normal" font="default" size="100%">36599181</style></accession-num><notes><style face="normal" font="default" size="100%">Panoutsopoulou, KonstantinaMagkou, ParaskeviDreyer, TobiasDorn, JuliaObermayr, EvaMahner, Svenvan Gorp, ToonBraicu, IoanaMagdolen, ViktorZeillinger, RobertAvgeris, MargaritisScorilas, AndreasengResearch Support, Non-U.S. Gov'tEngland2023/01/05 06:00Eur J Cancer. 2023 Feb;180:134-145. doi: 10.1016/j.ejca.2022.11.033. Epub 2022 Dec 10.</style></notes><auth-address><style face="normal" font="default" size="100%">Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.Clinical Research Unit, Department of Obstetrics and Gynecology, School of Medicine, Technical University of Munich, Munich, Germany.Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Vienna, Austria.Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.Department of Gynecology, Charite University Medicine, Campus Virchow, Berlin, Germany.Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece; Laboratory of Clinical Biochemistry - Molecular Diagnostics, Second Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, &quot;P. &amp; A. Kyriakou&quot; Children's Hospital, Athens, Greece. Electronic address: margaritis.avgeris@gmail.com.Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: ascorilas@biol.uoa.gr.</style></auth-address></record></records></xml>