The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35 Journal Article
| Authors: | 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.; Cheung, B. B.; Shi, L.; Wang, J. Y.; Simon, T.; Fischer, M.; Zhang, X. D.; Marshall, G. M.; Norris, M. D.; Haber, M.; Vandesompele, J.; Li, J.; Mestdagh, P.; Hannan, R. D.; Dinger, M. E.; Perini, G.; Liu, T. |
| Article 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. © 2019, The Author(s). |
| Keywords: | mitogen activated protein kinase; controlled study; protein expression; protein phosphorylation; unclassified drug; human cell; promoter region; doxorubicin; nonhuman; flow cytometry; cell proliferation; mass spectrometry; mouse; animal tissue; cell viability; gene; cell survival; mus; gene overexpression; apoptosis; gene expression; confocal microscopy; animal experiment; animal model; protein; protein stability; genetic transcription; tumor regression; carcinogenesis; rna; fluorescence in situ hybridization; genetic transfection; neuroblastoma; immunocytochemistry; protein synthesis; sequence alignment; chromatin immunoprecipitation; immunoblotting; rna translation; cellular distribution; polysome; down regulation; real time polymerase chain reaction; upregulation; dna microarray; gene dosage; tumor; transcription factor e2f1; ribosome protein; clonogenesis; rna sequence; protein rna binding; cell; peptides and proteins; cancer prognosis; gene knockdown; cell component; human; article; long untranslated rna; luciferase assay; 60s ribosomal protein l35; atp dependent rna helicase ddx42; dep domain containing 1b protein; heterogeneous nuclear ribonucleoprotein k; histone h1x; insulin like growth factor 2 mrna binding protein 1; interleukin enhancer binding factor 2; n cym protein; n myc proto oncogene protein; tubulin beta 2a chain; tubulin beta 2b chain |
| Journal Title: | Nature Communications |
| Volume: | 10 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-11-05 |
| Start Page: | 5026 |
| Language: | English |
| DOI: | 10.1038/s41467-019-12971-3 |
| PUBMED: | 31690716 |
| PROVIDER: | scopus |
| PMCID: | PMC6831662 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
