Abstract
Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression profiling revealed correlations between specific T-UCR expression levels and important clinicogenetic parameters such as MYCN amplification status. A functional genomics approach based on the integration of multi-level transcriptome data was adapted to gain insights into T-UCR functions. Assignments of T-UCRs to cellular processes such as TP53 response, differentiation and proliferation were verified using various cellular model systems. For the first time, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis.
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Acknowledgements
We are indebted to all the members of the SIOPEN and the GPOH for providing tumour samples or the clinical history of patients. This research was funded by the Gent University Research Fund (BOF 01D31406 to PM, BOF 01F07207 to FP, BOF 01Z09407 to J Vandesompele), the Belgian Kid's Fund and the Fondation pour la recherche Nuovo-Soldati (J Vermeulen), RD06/0020/0102 from RTICC/ISCIII to RN, the American Cancer Association to EF, the Swedish Cancer Society to MR, the Fund for Scientific Research (grant number: G.0198.08 and 31511809) and the Belgian Foundation Against Cancer, found of public interest (project SCIE2006-25). KDP is a postdoctoral researcher with the Fund for Scientific Research-Flanders. CK is supported by a doctoral grant from the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT - 081373). We acknowledge the support of the European Community under the FP6 (project: STREP: EET-pipeline, number: 037260) and FP7 (ONCOMIRS, grant agreement number 201102). This publication reflects only authors' views; the commission is not liable for any use that may be made of the information herein. This article presents research results of the Belgian programme of Interuniversity Poles of Attraction, initiated by the Belgian State, Prime Minister's Office, Science Policy Programming.
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Mestdagh, P., Fredlund, E., Pattyn, F. et al. An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours. Oncogene 29, 3583–3592 (2010). https://doi.org/10.1038/onc.2010.106
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DOI: https://doi.org/10.1038/onc.2010.106
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