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

Tanmoy Mondal; Prasanna Kumar Juvvuna; Agnete Kirkeby; Sanhita Mitra; Subazini Thankaswamy Kosalai; Larissa Traxler; Falk Hertwig; Sara Wernig-Zorc; Caroline Miranda; Lily Deland; Ruth Volland; Christoph Bartenhagen; Deniz Bartsch; Sashidhar Bandaru; Anne Engesser; Santhilal Subhash; Tommy Martinsson; Helena Carén; Levent M Akyürek; Leo Kurian; Meena Kanduri; Maite Huarte; Per Kogner; Matthias Fischer; Chandrasekhar Kanduri

doi:10.1016/j.ccell.2018.01.020

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

Tanmoy Mondal, Prasanna Kumar Juvvuna, Agnete Kirkeby, Sanhita Mitra, Subazini Thankaswamy Kosalai, Larissa Traxler, Falk Hertwig, Sara Wernig-Zorc, Caroline Miranda, Lily Deland, Ruth Volland, Christoph Bartenhagen, Deniz Bartsch, Sashidhar Bandaru, Anne Engesser, Santhilal Subhash, Tommy Martinsson, Helena Carén, Levent M Akyürek, Leo KurianMeena Kanduri, Maite Huarte, Per Kogner, Matthias Fischer, Chandrasekhar Kanduri

Laboratory

72 Citations (Scopus)

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. 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.

Original language	English
Journal	Cancer Cell
Volume	33
Issue number	3
Pages (from-to)	417-434.e7
ISSN	1535-6108
DOIs	https://doi.org/10.1016/j.ccell.2018.01.020
Publication status	Published - 12 Mar 2018

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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., Carén, H., Akyürek, L. M., ... Kanduri, C. (2018). Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis. Cancer Cell, 33(3), 417-434.e7. https://doi.org/10.1016/j.ccell.2018.01.020

Mondal, T, Juvvuna, PK, Kirkeby, A, Mitra, S, Kosalai, ST, 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, Carén, H, Akyürek, LM, Kurian, L, Kanduri, M, Huarte, M, Kogner, P, Fischer, M & Kanduri, C 2018, 'Sense-Antisense lncRNA Pair Encoded by Locus 6p22.3 Determines Neuroblastoma Susceptibility via the USP36-CHD7-SOX9 Regulatory Axis', Cancer Cell, vol. 33, no. 3, pp. 417-434.e7. https://doi.org/10.1016/j.ccell.2018.01.020

@article{9ee788104bd343c78e2a135c55f5b085,

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

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. 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.",

author = "Tanmoy Mondal and Juvvuna, {Prasanna Kumar} and Agnete Kirkeby and Sanhita Mitra and Kosalai, {Subazini Thankaswamy} and Larissa Traxler and Falk Hertwig and Sara Wernig-Zorc and Caroline Miranda and Lily Deland and Ruth Volland and Christoph Bartenhagen and Deniz Bartsch and Sashidhar Bandaru and Anne Engesser and Santhilal Subhash and Tommy Martinsson and Helena Car{\'e}n and Aky{\"u}rek, {Levent M} and Leo Kurian and Meena Kanduri and Maite Huarte and Per Kogner and Matthias Fischer and Chandrasekhar Kanduri",

year = "2018",

month = mar,

day = "12",

doi = "10.1016/j.ccell.2018.01.020",

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volume = "33",

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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

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 -

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

Abstract

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