HOME / PUBLICATIONS /

tRNA-derived small RNA 3'U-tRF(ValCAC) promotes tumour migration and early progression in ovarian cancer

Citation:

Panoutsopoulou K, Magkou P, Dreyer T, Dorn J, Obermayr E, Mahner S, van Gorp T, Braicu I, Magdolen V, Zeillinger R, Avgeris M, Scorilas A. tRNA-derived small RNA 3'U-tRF(ValCAC) promotes tumour migration and early progression in ovarian cancer. European Journal of Cancer 2023;180:134-145.

Abstract:

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.

Notes:

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.