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

Pei Y. Liu; Andrew E. Tee; Giorgio Milazzo; Katherine M. Hannan; Jesper Maag; Sujanna Mondal; Bernard Atmadibrata; Nenad Bartonicek; Hui Peng; Nicholas Ho; Chelsea Mayoh; Roberto Ciaccio; Yuting Sun; Michelle J. Henderson; Jixuan Gao; Celine Everaert; Amy J. Hulme; Matthew Wong; Qing Lan; Belamy B. Cheung; Leming Shi; Jenny Y. Wang; Thorsten Simon; Matthias Fischer; Xu D. Zhang; Glenn M. Marshall; Murray D. Norris; Michelle Haber; Jo Vandesompele; Jinyan Li; Pieter Mestdagh; Ross D. Hannan; Marcel E. Dinger; Giovanni Perini; Tao Liu

doi:10.1038/s41467-019-12971-3

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

Pei Y. Liu, Andrew E. Tee, Giorgio Milazzo, Katherine M. Hannan, Jesper Maag, Sujanna Mondal, Bernard Atmadibrata, Nenad Bartonicek, Hui Peng, Nicholas Ho, Chelsea Mayoh, Roberto Ciaccio, Yuting Sun, Michelle J. Henderson, Jixuan Gao, Celine Everaert, Amy J. Hulme, Matthew Wong, Qing Lan, Belamy B. CheungLeming Shi, Jenny Y. Wang, Thorsten Simon, Matthias Fischer, Xu D. Zhang, Glenn M. Marshall, Murray D. Norris, Michelle Haber, Jo Vandesompele, Jinyan Li, Pieter Mestdagh, Ross D. Hannan, Marcel E. Dinger, Giovanni Perini, Tao Liu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	5026
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12971-3
Publication status	Published - 1 Dec 2019

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Liu, P. Y., Tee, A. E., Milazzo, G., Hannan, K. M., Maag, J., Mondal, S., Atmadibrata, B., Bartonicek, N., Peng, H., Ho, N., Mayoh, C., Ciaccio, R., Sun, Y., Henderson, M. J., Gao, J., Everaert, C., Hulme, A. J., Wong, M., Lan, Q., ... Liu, T. (2019). The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35. Nature Communications, 10(1), Article 5026. https://doi.org/10.1038/s41467-019-12971-3

@article{66b8c5f53f15420e9091db48a9922250,

title = "The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35",

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.",

author = "Liu, {Pei Y.} and Tee, {Andrew E.} and Giorgio Milazzo and Hannan, {Katherine M.} and Jesper Maag and Sujanna Mondal and Bernard Atmadibrata and Nenad Bartonicek and Hui Peng and Nicholas Ho and Chelsea Mayoh and Roberto Ciaccio and Yuting Sun and Henderson, {Michelle J.} and Jixuan Gao and Celine Everaert and Hulme, {Amy J.} and Matthew Wong and Qing Lan and Cheung, {Belamy B.} and Leming Shi and Wang, {Jenny Y.} and Thorsten Simon and Matthias Fischer and Zhang, {Xu D.} and Marshall, {Glenn M.} and Norris, {Murray D.} and Michelle Haber and Jo Vandesompele and Jinyan Li and Pieter Mestdagh and Hannan, {Ross D.} and Dinger, {Marcel E.} and Giovanni Perini and Tao Liu",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-12971-3",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

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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 2019, 'The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35', Nature Communications, vol. 10, no. 1, 5026. https://doi.org/10.1038/s41467-019-12971-3

TY - JOUR

T1 - The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35

AU - Liu, Pei Y.

AU - Tee, Andrew E.

AU - Milazzo, Giorgio

AU - Hannan, Katherine M.

AU - Maag, Jesper

AU - Mondal, Sujanna

AU - Atmadibrata, Bernard

AU - Bartonicek, Nenad

AU - Peng, Hui

AU - Ho, Nicholas

AU - Mayoh, Chelsea

AU - Ciaccio, Roberto

AU - Sun, Yuting

AU - Henderson, Michelle J.

AU - Gao, Jixuan

AU - Everaert, Celine

AU - Hulme, Amy J.

AU - Wong, Matthew

AU - Lan, Qing

AU - Cheung, Belamy B.

AU - Shi, Leming

AU - Wang, Jenny Y.

AU - Simon, Thorsten

AU - Fischer, Matthias

AU - Zhang, Xu D.

AU - Marshall, Glenn M.

AU - Norris, Murray D.

AU - Haber, Michelle

AU - Vandesompele, Jo

AU - Li, Jinyan

AU - Mestdagh, Pieter

AU - Hannan, Ross D.

AU - Dinger, Marcel E.

AU - Perini, Giovanni

AU - Liu, Tao

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-019-12971-3

DO - 10.1038/s41467-019-12971-3

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5026

ER -

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

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