TY - JOUR
T1 - Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis
AU - Mondal, Tanmoy
AU - Juvvuna, Prasanna Kumar
AU - Kirkeby, Agnete
AU - Mitra, Sanhita
AU - Kosalai, Subazini Thankaswamy
AU - Traxler, Larissa
AU - Hertwig, Falk
AU - Wernig-Zorc, Sara
AU - Miranda, Caroline
AU - Deland, Lily
AU - Volland, Ruth
AU - Bartenhagen, Christoph
AU - Bartsch, Deniz
AU - Bandaru, Sashidhar
AU - Engesser, Anne
AU - Subhash, Santhilal
AU - Martinsson, Tommy
AU - Carén, Helena
AU - Akyürek, Levent M
AU - Kurian, Leo
AU - Kanduri, Meena
AU - Huarte, Maite
AU - Kogner, Per
AU - Fischer, Matthias
AU - Kanduri, Chandrasekhar
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/3/12
Y1 - 2018/3/12
N2 - 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. Mondal et al. show a sense/antisense lncRNA pair expressed from the neuroblastoma (NB) risk-associated 6p22.3 locus is important for retinoic acid-induced NB differentiation gene-regulatory network by controlling CHD7 stability via modulating the cellular localization of the ubiquitin specific protease USP36.
AB - 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. Mondal et al. show a sense/antisense lncRNA pair expressed from the neuroblastoma (NB) risk-associated 6p22.3 locus is important for retinoic acid-induced NB differentiation gene-regulatory network by controlling CHD7 stability via modulating the cellular localization of the ubiquitin specific protease USP36.
U2 - 10.1016/j.ccell.2018.01.020
DO - 10.1016/j.ccell.2018.01.020
M3 - Journal article
C2 - 29533783
SN - 1535-6108
VL - 33
SP - 417-434.e7
JO - Cancer Cell
JF - Cancer Cell
IS - 3
ER -