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000277340 1001_ $$00000-0001-9619-4329$$aFuchs, Steffen$$b0
000277340 245__ $$aDefining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN.
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000277340 520__ $$aCircular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.
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000277340 7001_ $$aDanßmann, Clara$$b1
000277340 7001_ $$aKlironomos, Filippos$$b2
000277340 7001_ $$aWinkler, Annika$$b3
000277340 7001_ $$00000-0002-4573-9939$$aFallmann, Jörg$$b4
000277340 7001_ $$00000-0003-3630-3727$$aKruetzfeldt, Louisa-Marie$$b5
000277340 7001_ $$aSzymansky, Annabell$$b6
000277340 7001_ $$aNaderi, Julian$$b7
000277340 7001_ $$00000-0002-5928-9449$$aBernhart, Stephan H$$b8
000277340 7001_ $$0P:(DE-HGF)0$$aGrunewald, Laura$$b9
000277340 7001_ $$00000-0003-0773-4114$$aHelmsauer, Konstantin$$b10
000277340 7001_ $$00000-0002-2555-0178$$aRodriguez-Fos, Elias$$b11
000277340 7001_ $$00000-0002-7049-534X$$aKirchner, Marieluise$$b12
000277340 7001_ $$00000-0002-2245-528X$$aMertins, Philipp$$b13
000277340 7001_ $$00000-0002-7872-1997$$aAstrahantseff, Kathy$$b14
000277340 7001_ $$aSuenkel, Christin$$b15
000277340 7001_ $$00000-0003-1471-1295$$aToedling, Joern$$b16
000277340 7001_ $$00000-0002-2610-0144$$aMeggetto, Fabienne$$b17
000277340 7001_ $$0P:(DE-He78)a244aa021112b9002419791434bbc71c$$aRemke, Marc$$b18$$udkfz
000277340 7001_ $$aStadler, Peter F$$b19
000277340 7001_ $$aHundsdoerfer, Patrick$$b20
000277340 7001_ $$00000-0002-6115-4893$$aDeubzer, Hedwig E$$b21
000277340 7001_ $$00000-0002-8406-5412$$aKünkele, Annette$$b22
000277340 7001_ $$00000-0001-7737-2142$$aLang, Peter$$b23
000277340 7001_ $$aFuchs, Jörg$$b24
000277340 7001_ $$00000-0003-1534-778X$$aHenssen, Anton G$$b25
000277340 7001_ $$00000-0003-3476-8184$$aEggert, Angelika$$b26
000277340 7001_ $$00000-0002-4785-4332$$aRajewsky, Nikolaus$$b27
000277340 7001_ $$00000-0003-4784-6516$$aHertwig, Falk$$b28
000277340 7001_ $$0P:(DE-He78)91317a47fc8532e3daf0d0b362c2a27e$$aSchulte, Johannes$$b29
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