Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN.
In: Nature Communications, Jg. 14 (2023-07-04), Heft 1, S. 1-21
academicJournal
Zugriff:
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. The role of circular RNAs (circRNAs) in modulating gene expression in cancer remains to be investigated. Here, the authors perform whole transcriptome sequencing in 104 primary neuroblastomas and reveal the involvement of MYCN in regulating circRNAs. [ABSTRACT FROM AUTHOR]
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Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN.
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Autor/in / Beteiligte Person: | Fuchs, Steffen ; Danßmann, Clara ; Klironomos, Filippos ; Winkler, Annika ; Fallmann, Jörg ; Kruetzfeldt, Louisa-Marie ; Szymansky, Annabell ; Naderi, Julian ; Bernhart, Stephan H. ; Grunewald, Laura ; Helmsauer, Konstantin ; Rodriguez-Fos, Elias ; Kirchner, Marieluise ; Mertins, Philipp ; Astrahantseff, Kathy ; Suenkel, Christin ; Toedling, Joern ; Meggetto, Fabienne ; Remke, Marc ; Stadler, Peter F. |
Zeitschrift: | Nature Communications, Jg. 14 (2023-07-04), Heft 1, S. 1-21 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-023-38747-4 |
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