The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.

Liu, PY; Tee, AE; Milazzo, G; Hannan, KM; Maag, J; Mondal, S; Atmadibrata, B; Bartonicek, N; Peng, H; Ho, N; Mayoh, C; Ciaccio, R; Sun, Y; Henderson, MJ; Gao, J; Everaert, C; Hulme, AJ; Wong, M; Lan, Q; Cheung, BB; Shi, L; Wang, JY; Simon, T; Fischer, M; Zhang, XD; Marshall, GM; Norris, MD; Haber, M; Vandesompele, J; Li, J; Mestdagh, P; Hannan, RD; Dinger, ME; Perini, G; Liu, T

The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.

Liu, PY Tee, AE Milazzo, G Hannan, KM Maag, J Mondal, S Atmadibrata, B Bartonicek, N Peng, H Ho, N Mayoh, C Ciaccio, R Sun, Y Henderson, MJ Gao, J Everaert, C Hulme, AJ Wong, M Lan, Q Cheung, BB Shi, L Wang, JY Simon, T Fischer, M Zhang, XD Marshall, GM Norris, MD Haber, M Vandesompele, J Li, J

Mestdagh, P Hannan, RD Dinger, ME Perini, G Liu, T

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Publisher:: Springer Science and Business Media LLC
Publication Type:: Journal Article
Citation:: Nature communications, 2019, 10, (1), pp. 5026
Issue Date:: 2019-11-05

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Field	Value	Language
dc.contributor.author	Liu, PY
dc.contributor.author	Tee, AE
dc.contributor.author	Milazzo, G
dc.contributor.author	Hannan, KM
dc.contributor.author	Maag, J
dc.contributor.author	Mondal, S
dc.contributor.author	Atmadibrata, B
dc.contributor.author	Bartonicek, N
dc.contributor.author	Peng, H
dc.contributor.author	Ho, N
dc.contributor.author	Mayoh, C
dc.contributor.author	Ciaccio, R
dc.contributor.author	Sun, Y
dc.contributor.author	Henderson, MJ
dc.contributor.author	Gao, J
dc.contributor.author	Everaert, C
dc.contributor.author	Hulme, AJ
dc.contributor.author	Wong, M
dc.contributor.author	Lan, Q
dc.contributor.author	Cheung, BB
dc.contributor.author	Shi, L
dc.contributor.author	Wang, JY
dc.contributor.author	Simon, T
dc.contributor.author	Fischer, M
dc.contributor.author	Zhang, XD
dc.contributor.author	Marshall, GM
dc.contributor.author	Norris, MD
dc.contributor.author	Haber, M
dc.contributor.author	Vandesompele, J
dc.contributor.author	Li, J https://orcid.org/0000-0003-1833-7413
dc.contributor.author	Mestdagh, P
dc.contributor.author	Hannan, RD
dc.contributor.author	Dinger, ME
dc.contributor.author	Perini, G
dc.contributor.author	Liu, T
dc.date.accessioned	2021-04-26T05:06:56Z
dc.date.available	2019-10-09
dc.date.available	2021-04-26T05:06:56Z
dc.date.issued	2019-11-05
dc.identifier.citation	Nature communications, 2019, 10, (1), pp. 5026
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/148380
dc.description.abstract	The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	Nature communications
dc.relation.isbasedon	10.1038/s41467-019-12971-3
dc.rights	This is a post-peer-review, pre-copyedit version of an article published in Nature communications. The final authenticated version is available online at: https://dx.doi.org/10.1038/s41467-019-12971-3.	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Humans
dc.subject.mesh	Mice, Nude
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	GTPase-Activating Proteins
dc.subject.mesh	Ribosomal Proteins
dc.subject.mesh	Prognosis
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Cell Survival
dc.subject.mesh	Protein Biosynthesis
dc.subject.mesh	Transcription, Genetic
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Up-Regulation
dc.subject.mesh	Female
dc.subject.mesh	E2F1 Transcription Factor
dc.subject.mesh	Protein Stability
dc.subject.mesh	RNA, Long Noncoding
dc.subject.mesh	Carcinogenesis
dc.subject.mesh	N-Myc Proto-Oncogene Protein
dc.subject.mesh	Animals
dc.subject.mesh	Carcinogenesis
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Cell Survival
dc.subject.mesh	E2F1 Transcription Factor
dc.subject.mesh	Female
dc.subject.mesh	GTPase-Activating Proteins
dc.subject.mesh	Gene Expression Regulation, Neoplastic
dc.subject.mesh	Humans
dc.subject.mesh	Mice, Inbred BALB C
dc.subject.mesh	Mice, Nude
dc.subject.mesh	N-Myc Proto-Oncogene Protein
dc.subject.mesh	Neuroblastoma
dc.subject.mesh	Prognosis
dc.subject.mesh	Protein Biosynthesis
dc.subject.mesh	Protein Stability
dc.subject.mesh	RNA, Long Noncoding
dc.subject.mesh	Ribosomal Proteins
dc.subject.mesh	Transcription, Genetic
dc.subject.mesh	Up-Regulation
dc.title	The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/A/DRsch The Data Science Institute
utslib.copyright.status	open_access	*
dc.date.updated	2021-04-26T05:06:51Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	10
utslib.citation.issue	1

Abstract:

The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/148380