array(14 items) uid => 893 (integer) title => 'Defining the landscape of circular RNAs in neuroblastoma unveils a global su
ppressive function of MYCN' (102 chars) abstract => 'Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving fu
nctions have been identified for single circRNAs, how they modulate gene exp
ression 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 demon
strate 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. Compar
isons to other cancers identify 25 circRNAs that are specifically upregulate
d 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 molecula
r mechanisms, which explain their contribution to neuroblastoma pathogenesis
.' (1141 chars) authors => array(30 items) 0 => array(3 items) last_name => 'Fuchs' (5 chars) first_name => 'Steffen' (7 chars) sorting => 1 (integer) 1 => array(3 items) last_name => 'Danßmann' (9 chars) first_name => 'Clara' (5 chars) sorting => 2 (integer) 2 => array(3 items) last_name => 'Klironomos' (10 chars) first_name => 'Filippos' (8 chars) sorting => 3 (integer) 3 => array(3 items) last_name => 'Winkler' (7 chars) first_name => 'Annika' (6 chars) sorting => 4 (integer) 4 => array(3 items) last_name => 'Fallmann' (8 chars) first_name => 'Jörg' (5 chars) sorting => 5 (integer) 5 => array(3 items) last_name => 'Krützfeldt' (11 chars) first_name => 'Louisa Marie' (12 chars) sorting => 6 (integer) 6 => array(3 items) last_name => 'Szymansky' (9 chars) first_name => 'Annabell' (8 chars) sorting => 7 (integer) 7 => array(3 items) last_name => 'Naderi' (6 chars) first_name => 'Julian' (6 chars) sorting => 8 (integer) 8 => array(3 items) last_name => 'Bernhart' (8 chars) first_name => 'Stephan H. F.' (14 chars) sorting => 9 (integer) 9 => array(3 items) last_name => 'Grunewald' (9 chars) first_name => 'Laura' (5 chars) sorting => 10 (integer) 10 => array(3 items) last_name => 'Helmsaür' (9 chars) first_name => 'Konstantin' (10 chars) sorting => 11 (integer) 11 => array(3 items) last_name => 'Rodrigüz Fos' (13 chars) first_name => 'Elias' (5 chars) sorting => 12 (integer) 12 => array(3 items) last_name => 'Kirchner' (8 chars) first_name => 'Marieluise' (10 chars) sorting => 13 (integer) 13 => array(3 items) last_name => 'Mertins' (7 chars) first_name => 'Philipp' (7 chars) sorting => 14 (integer) 14 => array(3 items) last_name => 'Astrahantseff' (13 chars) first_name => 'Kathy' (5 chars) sorting => 15 (integer) 15 => array(3 items) last_name => 'Sünkel' (7 chars) first_name => 'Christin' (8 chars) sorting => 16 (integer) 16 => array(3 items) last_name => 'Todling' (7 chars) first_name => 'Jorn' (4 chars) sorting => 17 (integer) 17 => array(3 items) last_name => 'Meggetto' (8 chars) first_name => 'Fabienne' (8 chars) sorting => 18 (integer) 18 => array(3 items) last_name => 'Remke' (5 chars) first_name => 'Marc' (4 chars) sorting => 19 (integer) 19 => array(3 items) last_name => 'Stadler' (7 chars) first_name => 'Peter Florian' (13 chars) sorting => 20 (integer) 20 => array(3 items) last_name => 'Hundsdorfer' (11 chars) first_name => 'Patrick' (7 chars) sorting => 21 (integer) 21 => array(3 items) last_name => 'Deubzer' (7 chars) first_name => 'Hedwig E.' (9 chars) sorting => 22 (integer) 22 => array(3 items) last_name => 'Künkele' (8 chars) first_name => 'Annette' (7 chars) sorting => 23 (integer) 23 => array(3 items) last_name => 'Lang' (4 chars) first_name => 'Peter' (5 chars) sorting => 24 (integer) 24 => array(3 items) last_name => 'Fuchs' (5 chars) first_name => 'Jörg' (5 chars) sorting => 25 (integer) 25 => array(3 items) last_name => 'Henssen' (7 chars) first_name => 'Anton G.' (8 chars) sorting => 26 (integer) 26 => array(3 items) last_name => 'Eggert' (6 chars) first_name => 'Angelika' (8 chars) sorting => 27 (integer) 27 => array(3 items) last_name => 'Rajewsky' (8 chars) first_name => 'Nikolaus' (8 chars) sorting => 28 (integer) 28 => array(3 items) last_name => 'Hertwig' (7 chars) first_name => 'Falk' (4 chars) sorting => 29 (integer) 29 => array(3 items) last_name => 'Schulte' (7 chars) first_name => 'Johannes H.' (11 chars) sorting => 30 (integer) type => '0' (1 chars) keywords => 'General Physics and Astronomy, General Biochemistry, Genetics and Molecular
Biology, General Chemistry, Multidisciplinary' (121 chars) year => 2023 (integer) affiliation => 0 (integer) link_paper => 'https://www.nature.com/articles/s41467-023-38747-4.pdf' (54 chars) link_supplements => '' (0 chars) file_published => 0 (integer) journal => 'Nature Communications' (21 chars) doi => '10.1038/s41467-023-38747-4' (26 chars) preprint => '-1' (2 chars)
Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN
2023: Steffen Fuchs; Clara Danßmann; Filippos Klironomos; Annika Winkler; Jörg Fallmann; Louisa Marie Krützfeldt; Annabell Szymansky; Julian Naderi; Stephan H. F. Bernhart; Laura Grunewald; Konstantin Helmsaür; Elias Rodrigüz Fos; Marieluise Kirchner; Philipp Mertins; Kathy Astrahantseff; Christin Sünkel; Jorn Todling; Fabienne Meggetto; Marc Remke; Peter Florian Stadler; Patrick Hundsdorfer; Hedwig E. Deubzer; Annette Künkele; Peter Lang; Jörg Fuchs; Anton G. Henssen; Angelika Eggert; Nikolaus Rajewsky; Falk Hertwig; Johannes H. SchulteIn: Nature Communications Link to Publication DOI: 10.1038/s41467-023-38747-4
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: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary