dc.contributor.author
Fuchs, Steffen
dc.contributor.author
Danßmann, Clara
dc.contributor.author
Klironomos, Filippos
dc.contributor.author
Winkler, Annika
dc.contributor.author
Fallmann, Jörg
dc.contributor.author
Kruetzfeldt, Louisa-Marie
dc.contributor.author
Szymansky, Annabell
dc.contributor.author
Naderi, Julian
dc.contributor.author
Bernhart, Stephan H.
dc.contributor.author
Grunewald, Laura
dc.contributor.author
Helmsauer, Konstantin
dc.contributor.author
Rodriguez-Fos, Elias
dc.contributor.author
Kirchner, Marieluise
dc.contributor.author
Mertins, Philipp
dc.contributor.author
Astrahantseff, Kathy
dc.contributor.author
Suenkel, Christin
dc.contributor.author
Toedling, Joern
dc.contributor.author
Meggetto, Fabienne
dc.contributor.author
Remke, Marc
dc.contributor.author
Stadler, Peter F.
dc.contributor.author
Hundsdoerfer, Patrick
dc.contributor.author
Deubzer, Hedwig E.
dc.contributor.author
Künkele, Annette
dc.contributor.author
Lang, Peter
dc.contributor.author
Fuchs, Jörg
dc.contributor.author
Henssen, Anton G.
dc.contributor.author
Eggert, Angelika
dc.contributor.author
Rajewsky, Nikolaus
dc.contributor.author
Hertwig, Falk
dc.contributor.author
Schulte, Johannes H.
dc.date.accessioned
2023-10-11T11:26:25Z
dc.date.available
2023-10-11T11:26:25Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40986
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-40707
dc.description.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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
circular RNA
en
dc.subject
neuroblastoma
en
dc.subject
gene expression regulation
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
3936
dcterms.bibliographicCitation.doi
10.1038/s41467-023-38747-4
dcterms.bibliographicCitation.journaltitle
Nature Communications
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.volume
14
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
37402719
dcterms.isPartOf.eissn
2041-1723