MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001001441	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 non-coding RNAs (lncRNAs), on the way MYC is able to influence cellular transcriptome. To this aim we have intersected RNA-sequencing data from two MYC-inducible cell lines and from a cohort of 91 mature B-cell lymphomas carrying, or not carrying, genetic variants resulting in MYC over-expression. By this approach, 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 MINCR, for MYC-Induced long Non-Coding RNA, showing a strong correlation with MYC expression in MYC-positive lymphomas and also in pancreatic ductal adenocarcinomas. To understand its cellular role we performed RNA interference (RNAi) experiments and found that MINCR knock-down is associated with a reduction in cellular viability, due to an impairment in cell cycle progression. Differential gene expression analysis following RNAi showed a strongly significant enrichment of cell cycle genes among the genes down-regulate following MINCR knock-down. Interestingly these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of MYC transcriptional program. Accordingly, following MINCR knock-down, we observed a reduction in the binding of MYC to the promoters of selected cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.	Illumina HiSeq 2000 Illumina HiSeq 2500	49
EGAD00001001598	RNA-sequencing data from teh hT-RPE-MycER cell line after MYC activation and after MINCR knock-down in conditions of MYC ON or OFF	Illumina HiSeq 2500	18

Publications	Citations
MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells. Doose G, Haake A, Bernhart SH, López C, Duggimpudi S, Wojciech F, Bergmann AK, Borkhardt A, Burkhardt B, Claviez A, Dimitrova L, Haas S, Hoell JI, Hummel M, Karsch D, Klapper W, Kleo K, Kretzmer H, Kreuz M, Küppers R, Lawerenz C, Lenze D, Loeffler M, Mantovani-Löffler L, Möller P, Ott G, Richter J, Rohde M, Rosenstiel P, Rosenwald A, Schilhabel M, Schneider M, Scholz I, Stilgenbauer S, Stunnenberg HG, Szczepanowski M, Trümper L, Weniger MA, ICGC MMML-Seq Consortium, Hoffmann S, Siebert R, Iaccarino I. Proc Natl Acad Sci U S A 112: 2015 E5261-70	70

Publications

Citations

MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells.
Doose G, Haake A, Bernhart SH, López C, Duggimpudi S, Wojciech F, Bergmann AK, Borkhardt A, Burkhardt B, Claviez A, Dimitrova L, Haas S, Hoell JI, Hummel M, Karsch D, Klapper W, Kleo K, Kretzmer H, Kreuz M, Küppers R, Lawerenz C, Lenze D, Loeffler M, Mantovani-Löffler L, Möller P, Ott G, Richter J, Rohde M, Rosenstiel P, Rosenwald A, Schilhabel M, Schneider M, Scholz I, Stilgenbauer S, Stunnenberg HG, Szczepanowski M, Trümper L, Weniger MA, ICGC MMML-Seq Consortium, Hoffmann S, Siebert R, Iaccarino I. Proc Natl Acad Sci U S A 112: 2015 E5261-70