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Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN

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Item Type:Article
Title:Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN
Creators Name:Fuchs, S. and Danßmann, C. and Klironomos, F. and Winkler, A. and Fallmann, J. and Kruetzfeldt, L.M. and Szymansky, A. and Naderi, J. and Bernhart, S.H. and Grunewald, L. and Helmsauer, K. and Rodriguez-Fos, E. and Kirchner, M. and Mertins, P. and Astrahantseff, K. and Suenkel, C. and Toedling, J. and Meggetto, F. and Remke, M. and Stadler, P.F. and Hundsdoerfer, P. and Deubzer, H.E. and Künkele, A. and Lang, P. and Fuchs, J. and Henssen, A.G. and Eggert, A. and Rajewsky, N. and Hertwig, F. and Schulte, J.H.
Abstract:Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.
Keywords:Tumor Cell Line, Neoplastic Gene Expression Regulation, N-Myc Proto-Oncogene Protein, Neuroblastoma, RNA, Circular RNA / Genetics
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:3936
Date:4 July 2023
Official Publication:https://doi.org/10.1038/s41467-023-38747-4
PubMed:View item in PubMed

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