Detalle Publicación

Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis

Autores: Mondal, T.; Juvvuna, P. K.; Kirkeby, A.; Mitra, S.; Kosalai, S. T.; Traxler, L.; Hertwig, F.; Wernig-Zorc, S.; Miranda, C.; Deland, L.; Volland, R.; Bartenhagen, C.; Bartsch, D.; Bandaru, S.; Engesser, A.; Subhash, S.; Martinsson, T.; Caren, H.; Akyurek, L. M.; Kurian, L.; Kanduri, M. (Autor de correspondencia); Huarte Martínez, Maite; Kogner, P.; Fischer, M.; Kanduri, C.
Título de la revista: CANCER CELL
ISSN: 1535-6108
Volumen: 33
Número: 3
Páginas: 417 - +
Fecha de publicación: 2018
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.