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 () and Tao Liu ()
Additional contact information
Pei Y. Liu: Children’s Cancer Institute Australia for Medical Research
Andrew E. Tee: Children’s Cancer Institute Australia for Medical Research
Giorgio Milazzo: University of Bologna
Katherine M. Hannan: The Australian National University
Jesper Maag: Garvan Institute of Medical Research, Sydney
Sujanna Mondal: Children’s Cancer Institute Australia for Medical Research
Bernard Atmadibrata: Children’s Cancer Institute Australia for Medical Research
Nenad Bartonicek: Garvan Institute of Medical Research, Sydney
Hui Peng: University of Technology Sydney
Nicholas Ho: Children’s Cancer Institute Australia for Medical Research
Chelsea Mayoh: Children’s Cancer Institute Australia for Medical Research
Roberto Ciaccio: University of Bologna
Yuting Sun: Children’s Cancer Institute Australia for Medical Research
Michelle J. Henderson: Children’s Cancer Institute Australia for Medical Research
Jixuan Gao: Children’s Cancer Institute Australia for Medical Research
Celine Everaert: Ghent University
Amy J. Hulme: Children’s Cancer Institute Australia for Medical Research
Matthew Wong: Children’s Cancer Institute Australia for Medical Research
Qing Lan: the Second Affiliated Hospital of Soochow University
Belamy B. Cheung: Children’s Cancer Institute Australia for Medical Research
Leming Shi: Fudan University
Jenny Y. Wang: Children’s Cancer Institute Australia for Medical Research
Thorsten Simon: University Hospital, University of Cologne
Matthias Fischer: University of Cologne
Xu D. Zhang: University of Newcastle
Glenn M. Marshall: Children’s Cancer Institute Australia for Medical Research
Murray D. Norris: Children’s Cancer Institute Australia for Medical Research
Michelle Haber: Children’s Cancer Institute Australia for Medical Research
Jo Vandesompele: Ghent University
Jinyan Li: University of Technology Sydney
Pieter Mestdagh: Ghent University
Ross D. Hannan: The Australian National University
Marcel E. Dinger: Garvan Institute of Medical Research, Sydney
Giovanni Perini: University of Bologna
Tao Liu: Children’s Cancer Institute Australia for Medical Research

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12971-3

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