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         headline:The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35
         description: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. MYCN amplification is common in neuroblastomas. Here, the authors identify a long noncoding RNA, lncNB1 in these cancers and show that it promotes tumorigenesis by binding to ribosomal protein, RPL35 to enhance E2F1 and DEPDC1B protein synthesis, which phosphorylates ERK to stabilise N-Myc.
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      headline:The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35
      description: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. MYCN amplification is common in neuroblastomas. Here, the authors identify a long noncoding RNA, lncNB1 in these cancers and show that it promotes tumorigenesis by binding to ribosomal protein, RPL35 to enhance E2F1 and DEPDC1B protein synthesis, which phosphorylates ERK to stabilise N-Myc.
      datePublished:2019-11-05T00:00:00Z
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         Paediatric cancer
         Science
         Humanities and Social Sciences
         multidisciplinary
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      name:Qing Lan
      affiliation:
            name:the Second Affiliated Hospital of Soochow University
            address:
               name:Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
               type:PostalAddress
            type:Organization
      name:Belamy B. Cheung
      url:http://orcid.org/0000-0001-8784-860X
      affiliation:
            name:Children’s Cancer Institute Australia for Medical Research
            address:
               name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
               type:PostalAddress
            type:Organization
      name:Leming Shi
      affiliation:
            name:Fudan University
            address:
               name:State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Jenny Y. Wang
      url:http://orcid.org/0000-0002-1325-7943
      affiliation:
            name:Children’s Cancer Institute Australia for Medical Research
            address:
               name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
               type:PostalAddress
            type:Organization
      name:Thorsten Simon
      url:http://orcid.org/0000-0002-3425-8451
      affiliation:
            name:University Hospital, University of Cologne
            address:
               name:Department of Pediatric Oncology and Hematology, University Hospital, University of Cologne, Cologne, Germany
               type:PostalAddress
            type:Organization
      name:Matthias Fischer
      url:http://orcid.org/0000-0003-1363-1242
      affiliation:
            name:University of Cologne
            address:
               name:Department of Experimental Pediatric Oncology, University Hospital, University of Cologne, Cologne, Germany
               type:PostalAddress
            type:Organization
      name:Xu D. Zhang
      url:http://orcid.org/0000-0001-9457-8003
      affiliation:
            name:University of Newcastle
            address:
               name:School of Medicine and Public Health, Priority Research Centre for Cancer Research, University of Newcastle, Callaghan, Australia
               type:PostalAddress
            type:Organization
      name:Glenn M. Marshall
      affiliation:
            name:Children’s Cancer Institute Australia for Medical Research
            address:
               name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
               type:PostalAddress
            type:Organization
            name:Sydney Children’s Hospital
            address:
               name:Kids Cancer Centre, Sydney Children’s Hospital, Randwick, Australia
               type:PostalAddress
            type:Organization
      name:Murray D. Norris
      url:http://orcid.org/0000-0002-0632-4589
      affiliation:
            name:Children’s Cancer Institute Australia for Medical Research
            address:
               name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
               type:PostalAddress
            type:Organization
      name:Michelle Haber
      url:http://orcid.org/0000-0003-2036-8817
      affiliation:
            name:Children’s Cancer Institute Australia for Medical Research
            address:
               name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
               type:PostalAddress
            type:Organization
      name:Jo Vandesompele
      url:http://orcid.org/0000-0001-6274-0184
      affiliation:
            name:Ghent University
            address:
               name:Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium
               type:PostalAddress
            type:Organization
      name:Jinyan Li
      url:http://orcid.org/0000-0003-1833-7413
      affiliation:
            name:University of Technology Sydney
            address:
               name:Advanced Analytics Institute, University of Technology Sydney, Broadway, Australia
               type:PostalAddress
            type:Organization
      name:Pieter Mestdagh
      url:http://orcid.org/0000-0001-7821-9684
      affiliation:
            name:Ghent University
            address:
               name:Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium
               type:PostalAddress
            type:Organization
      name:Ross D. Hannan
      url:http://orcid.org/0000-0002-2166-4493
      affiliation:
            name:The Australian National University
            address:
               name:Australian Cancer Research Foundation Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia
               type:PostalAddress
            type:Organization
            name:University of Melbourne
            address:
               name:Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia
               type:PostalAddress
            type:Organization
            name:University of Melbourne
            address:
               name:Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia
               type:PostalAddress
            type:Organization
            name:Monash University
            address:
               name:Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
               type:PostalAddress
            type:Organization
            name:University of Queensland
            address:
               name:School of Biomedical Sciences, University of Queensland, St Lucia, Australia
               type:PostalAddress
            type:Organization
      name:Marcel E. Dinger
      url:http://orcid.org/0000-0003-4423-934X
      affiliation:
            name:Garvan Institute of Medical Research, Sydney
            address:
               name:Garvan Institute of Medical Research, Sydney, Darlinghurst, Australia
               type:PostalAddress
            type:Organization
            name:University of New South Wales
            address:
               name:School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
               type:PostalAddress
            type:Organization
      name:Giovanni Perini
      affiliation:
            name:University of Bologna
            address:
               name:Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Tao Liu
      url:http://orcid.org/0000-0001-6244-7316
      affiliation:
            name:Children’s Cancer Institute Australia for Medical Research
            address:
               name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
      name:Australian Cancer Research Foundation Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia
      name:Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia
      name:Garvan Institute of Medical Research, Sydney, Darlinghurst, Australia
      name:Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Garvan Institute of Medical Research, Sydney, Darlinghurst, Australia
      name:Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Advanced Analytics Institute, University of Technology Sydney, Broadway, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Department of Pediatric Oncology and Hematology, University Hospital, University of Cologne, Cologne, Germany
      name:Department of Experimental Pediatric Oncology, University Hospital, University of Cologne, Cologne, Germany
      name:School of Medicine and Public Health, Priority Research Centre for Cancer Research, University of Newcastle, Callaghan, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Kids Cancer Centre, Sydney Children’s Hospital, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia
      name:Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium
      name:Advanced Analytics Institute, University of Technology Sydney, Broadway, Australia
      name:Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium
      name:Australian Cancer Research Foundation Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia
      name:Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia
      name:Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia
      name:Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
      name:School of Biomedical Sciences, University of Queensland, St Lucia, Australia
      name:Garvan Institute of Medical Research, Sydney, Darlinghurst, Australia
      name:School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
      name:Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
      name:Children’s Cancer Institute Australia for Medical Research, Randwick, Australia

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