Journal Article

DKFZ-2023-01348

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN.

Fuchs, S.DKFZ* ; Danßmann, C. ; Klironomos, F. ; Winkler, A. ; Fallmann, J. ; Kruetzfeldt, L.-M. ; Szymansky, A. ; Naderi, J. ; Bernhart, S. H. ; Grunewald, L.DKFZ* ; Helmsauer, K. ; Rodriguez-Fos, E. ; Kirchner, M. ; Mertins, P. ; Astrahantseff, K. ; Suenkel, C. ; Toedling, J.DKFZ* ; Meggetto, F. ; Remke, M.DKFZ* ; Stadler, P. F. ; Hundsdoerfer, P. ; Deubzer, H. E.DKFZ* ; Künkele, A.DKFZ* ; Lang, P. ; Fuchs, J. ; Henssen, A. G.DKFZ* ; Eggert, A.DKFZ* ; Rajewsky, N. ; Hertwig, F.DKFZ* ; Schulte, J.DKFZ*

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-38747-4

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.

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)
2. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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