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MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells
- Source :
- Proceedings of the National Academy of Sciences of the United States of America 112 (2015): E5261–E5270. doi:10.1073/pnas.1505753112, info:cnr-pdr/source/autori:Doose, Gero; Haake, Andrea; Bernhart, Stephan H.; Lopez, Cristina; Duggimpudi, Sujitha; Wojciech, Franziska; Bergmann, Anke K.; Borkhardt, Arndt; Burkhardt, Birgit; Claviez, Alexander; Dimitrova, Lora; Haas, Siegfried; Hoell, Jessica I.; Hummel, Michael; Karsch, Dennis; Klapper, Wolfram; Kleo, Karsten; Kretzmer, Helene; Kreuz, Markus; Kueppers, Ralf; Lawerenz, Chris; Lenze, Dido; Loeffler, Markus; Mantovani-Loeffler, Luisa; Moeller, Peter; Ott, German; Richter, Julia; Rohde, Marius; Rosenstiel, Philip; Rosenwald, Andreas; Schilhabel, Markus; Schneider, Markus; Scholz, Ingrid; Stilgenbauer, Stephan; Stunnenberg, Hendrik G.; Szczepanowski, Monika; Truemper, Lorenz; Weniger, Marc A.; Hoffmann, Steve; Siebert, Reiner; Iaccarino, Ingram/titolo:MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells/doi:10.1073%2Fpnas.1505753112/rivista:Proceedings of the National Academy of Sciences of the United States of America/anno:2015/pagina_da:E5261/pagina_a:E5270/intervallo_pagine:E5261–E5270/volume:112, Proceedings of the National Academy of Sciences USA, 112, E5261-E5270, Proceedings of the National Academy of Sciences USA, 112, 38, pp. E5261-E5270
- Publication Year :
- 2015
-
Abstract
- Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.
- Subjects :
- Lymphoma, B-Cell
Cell Survival
Molecular Sequence Data
Medizin
MYC
Biology
Cell Line
Transcriptome
Proto-Oncogene Proteins c-myc
lncRNA
RNA interference
Cell Line, Tumor
Neoplasms
Sequence Homology, Nucleic Acid
Humans
Gene Regulatory Networks
ddc:610
Letters
RNA, Small Interfering
Promoter Regions, Genetic
Molecular Biology
Transcription factor
In Situ Hybridization, Fluorescence
Gene knockdown
Multidisciplinary
Binding Sites
Base Sequence
B-cell lymphoma
Gene Expression Profiling
Cell Cycle
Promoter
Cell cycle
Cell Cycle Gene
Molecular biology
Burkitt Lymphoma
Chromatin
Cell biology
Gene Expression Regulation, Neoplastic
PNAS Plus
RNA, Long Noncoding
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 112
- Issue :
- 38
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....37d5d3c38f1e95c1c8372ce51b41b338