| Literature DB >> 29533783 |
Tanmoy Mondal1, Prasanna Kumar Juvvuna1, Agnete Kirkeby2, Sanhita Mitra1, Subazini Thankaswamy Kosalai1, Larissa Traxler3, Falk Hertwig4, Sara Wernig-Zorc1, Caroline Miranda1, Lily Deland1, Ruth Volland5, Christoph Bartenhagen5, Deniz Bartsch6, Sashidhar Bandaru1, Anne Engesser5, Santhilal Subhash1, Tommy Martinsson7, Helena Carén8, Levent M Akyürek9, Leo Kurian6, Meena Kanduri10, Maite Huarte11, Per Kogner12, Matthias Fischer5, Chandrasekhar Kanduri13.
Abstract
Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.Entities:
Keywords: CASC15; CHD7; NBAT1; SOX9; USP36; lncRNA; long noncoding RNA; neuroblastoma; neuronal differentiation; ubiquitination
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Year: 2018 PMID： 29533783 DOI： 10.1016/j.ccell.2018.01.020
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743