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Mastermind-like 3 controls proliferation and differentiation in neuroblastoma (ChIP-seq)

ABSTRACT: Neuroblastoma cell lines can differentiate upon retinoic acid (RA) treatment, a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen we identify the transcriptional coactivator Mastermind-like 3 (MAML3) as a gene whose ectopic expression confers resistance to RA. We find that MAML3 expression leads to loss of activation of a subset of RA target genes, which hampers RA-induced differentiation. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the retinoic acid receptor, suggesting a role for MAML3 in the regulation of these genes. In addition, MAML3 has RA independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. Our results indicate an important role for MAML3 in differentiation and proliferation of neuroblastomas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69119 | GEO | 2016/01/31

SECONDARY ACCESSION(S): PRJNA284602

REPOSITORIES: GEO

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Mastermind-like 3 controls proliferation and differentiation in neuroblastoma (RNA-seq)

Project description:Neuroblastoma cell lines can differentiate upon retinoic acid (RA) treatment, a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen we identify the transcriptional coactivator Mastermind-like 3 (MAML3) as a gene whose ectopic expression confers resistance to RA. We find that MAML3 expression leads to loss of activation of a subset of RA target genes, which hampers RA-induced differentiation. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the retinoic acid receptor, suggesting a role for MAML3 in the regulation of these genes. In addition, MAML3 has RA independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. Our results indicate an important role for MAML3 in differentiation and proliferation of neuroblastomas.

2016-01-31 | GSE69121 | GEO

RNA-seq of GSK-J4 Treated Neuroblastoma Cell Lines

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Lamin A/C is required for SHSY5Y neuroblastoma cell differentiation and its expression is linked to a less malignant phenotype.

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Project description:Our data demonstrate that CARM1 is required for transcriptional activation of a subset of retinoic acid (RA) target genes in J1 murine embryonic stem cells

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Gene expression from fibroblast-like synoviocytes (FLS) of three patients with rheumatoid arthritis (RA) that were cultured in four conditions: control medium (Basal), ATRA, TNF and ATRA+TNF.

Project description:The aim of this study was to investigate the response of FLS from RA patients to retinoic acid and retinoic acid combined with the central cytokine of RA, TNF.

2019-12-09 | GSE120785 | GEO

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