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

Author

Listed:
  • 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
    University of Melbourne)

  • Jesper Maag

    (Garvan Institute of Medical Research, Sydney
    Memorial Sloan Kettering Cancer Center)

  • 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
    Memorial Sloan Kettering Cancer Center)

  • 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
    Sydney Children’s Hospital)

  • 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
    University of Melbourne
    University of Melbourne
    Monash University)

  • Marcel E. Dinger

    (Garvan Institute of Medical Research, Sydney
    University of New South Wales)

  • Giovanni Perini

    (University of Bologna)

  • Tao Liu

    (Children’s Cancer Institute Australia for Medical Research)

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.

Suggested Citation

  • 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 & , 2019. "The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12971-3
    DOI: 10.1038/s41467-019-12971-3
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    Cited by:

    1. Minhui Chen & Andy Dahl, 2024. "A robust model for cell type-specific interindividual variation in single-cell RNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Ling Tao & Mahmoud A. Mohammad & Giorgio Milazzo & Myrthala Moreno-Smith & Tajhal D. Patel & Barry Zorman & Andrew Badachhape & Blanca E. Hernandez & Amber B. Wolf & Zihua Zeng & Jennifer H. Foster & , 2022. "MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Yage Ding & Cristina Tous & Jaehoon Choi & Jingyao Chen & Wilson W. Wong, 2024. "Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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