We analyed the gene expression profiles after knocking down MYCN or TFAP4. Results showed that transcription factor MYCN and TFAP4 commonly regulats a subset of genes that may contribute to neuroblastoma cells proliferation and migration.
MYCN promotes neuroblastoma malignancy by establishing a regulatory circuit with transcription factor AP4.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Age, Specimen part, Cell line, Treatment
View SamplesAmplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Cell line, Treatment
View SamplesAmplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Cell line, Treatment
View SamplesThe NF-B pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic beta cell dysfunction in the metabolic syndrome. While canonical NF-B signaling is well studied, there is little information on the divergent non-canonical NF-B pathway in the context of pancreatic islet dysfunction in diabetes. Here, we demonstrate that pharmacological activation of the non-canonical NF-B inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. Further, we identify NIK as a critical negative regulator of beta cell function as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of non-canonical NF-B components p100 to p52, and accumulation of RelB. Tumor necrosis factor (TNF) and receptor activator of NF-B ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive beta cell intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the non-canonical NF-B transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to beta cell failure. These studies reveal that NIK contributes a central mechanism for beta cell failure in diet-induced obesity.
Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity.
Specimen part, Treatment
View SamplesAdipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs.
Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.
Age, Specimen part
View SamplesRNA sequencing of PLZF+ and PLZF- ?d T cell subsets from adipose tissue for gene expression analysis Overall design: PLZF+ and PLZF- ?d T cells were sorted from adipose tissue of PLZF-GFP mice for subsequent RNA sequencing and gene-expression analysis. Two replicates for each subset pooled from 10 mice each were used for the study.
γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.
Sex, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
No sample metadata fields
View SamplesAn International Multi-Center Study to Define the Clinical Utility of MicroarrayBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study)
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Disease
View SamplesAn international standardization program towards the application of gene expression profiling in routine leukaemia diagnostics: The MILE study pre-phase.
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
No sample metadata fields
View Samples