MYCN and metabolic reprogramming in neuroblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Marie Arsenian-Henriksson
PROVIDER: PXD015755 | JPOST Repository | Thu Oct 31 00:00:00 GMT 2019
REPOSITORIES: jPOST
Dataset's files
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain-of-function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti-tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.
| S-EPMC8498874 | biostudies-literature
Project description:In order to investigate the effect of MondoA loss on the expression of Myc-dependent genes, we performed a microarray analysis from RNAs isolated from TET21N cells expressing either control (siControl) or MondoA (siMondoA) siRNAs either with (NT) or without (Doxy) induced N-Myc expression. TET21N cells were grown in medium with either Doxy (Myc-Off) or No Treatment (Myc-On), then transiently transfected with either non-specific siRNA or MondoA siRNA in replicates. Cells were then lysed and RNA isolated.
2015-01-01 | E-GEOD-55538 | biostudies-arrayexpress
Project description:Neuroblastoma (NB), a malignant embryonic tumor arising from primitive neural crest cells, accounts for more than 7% of malignancies and around 15% of cancer-related mortality in childhood. Better elucidating the mechanisms of tumorigenesis and aggressiveness is important for improving the therapeutic efficiencies of NB. To investigate the mechanisms underlying the tumor suppressive functions of RAR-related orphan receptor B (RORB), we employed the Illumina HiSeq X Ten as a discovery platform to analyze the genome-wide occupancy of RORB on target genes in human SK-N-BE(2) cells. The results showed that 1637 target genes were regulated by transcriptional regulator RORB, especially those involved in regulation of NF-κB signaling pathway. Furthermore, we validated the ChIP-seq results by real-time PCR with high identity. Overall, our results provided fundamental information about the genomic enrichment of RORB in human NB cells, and these findings will help us understand the pathogenesis of NB.
2025-12-10 | GSE305134 | GEO
Project description:Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. At diagnosis, around 70% of patients with metastatic disease present bone-marrow (BM) infiltration; however, the mechanism underlying this specific tropism has to be elucidated. Tumor-derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study was to identify an exosomal signature associated with NB metastatic BM dissemination. Therefore, we characterized the proteomic cargo of exosomes isolated from NB cell lines derived from primary tumor (PT) and BM metastasis. The comparison among all exosomal proteins showed 15 proteins exclusively present in PT, mainly involved in neuronal development, and 6 proteins in BM metastasis-derived exosomes related to cancer progression. Significant proteins obtained with t-test analysis, performed between the 2 groups (PT and BM metastasis), revealed that PT exosomes contain a higher level of proteins involved in extra-cellular matrix (ECM) assembly and adhesion, as well as in neuronal development. Exosomes isolated from BM metastasis showed proteins involved in ameboidal cell migration and mitochondrial activity. This work shows that proteomic profiling of NB-derived exosomes reflects the advanced tumor stage and may be considered as potential tumor biomarker
2018-07-05 | PXD005864 | Pride
Project description:Dysregulated pre-mRNA splicing and metabolism are two hallmarks of MYC-driven cancers. Pharmacological inhibition of both processes has been extensively investigated as potential therapeutic avenues in preclinical and clinical studies. However, how pre-mRNA splicing and metabolism are orchestrated in response to oncogenic stress and therapies is poorly understood. Here, we demonstrate that Jumonji Domain Containing 6, Arginine Demethylase and Lysine Hydroxylase, or JMJD6, acts as a hub connecting splicing and metabolism in MYC-driven neuroblastoma. JMJD6 cooperates with MYC in cellular transformation by physically interacting with RNA binding proteins involved in pre-mRNA splicing and protein homeostasis. Notably, JMJD6 controls the alternative splicing of two isoforms of glutaminase (GLS), namely kidney-type glutaminase (KGA) and glutaminase C (GAC), which are rate-limiting enzymes of glutaminolysis in the central carbon metabolism in neuroblastoma. Further, we show that JMJD6 is correlated with the anti-cancer activity of indisulam, a “molecular glue” that degrades splicing factor RBM39, which complexes with JMJD6. The indisulam-mediated cancer cell killing is at least partly dependent on the glutamine-related metabolic pathway mediated by JMJD6. Our findings reveal a cancer-promoting metabolic program is coupled with alternative pre-mRNA splicing through JMJD6, providing a rationale to target JMJD6 as a therapeutic avenue for treating MYC-driven cancers.
2024-03-11 | GSE248283 | GEO
Project description:Influenza infection is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry we found metabolic changes occurring after influenza infection in primary human respiratory cells, and validated infection associate increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen and high throughput titering that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in glucose and glutamine metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on viral entry or the early stages of viral replication. In a lethal infection model, BEZ235 significantly increased survival while reducing viral titer and respiratory distress. Here we show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention.
2017-05-24 | PXD006263 | Pride
Project description:In order to investigate the effect of MondoA loss on the expression of Myc-dependent genes, we performed a microarray analysis from RNAs isolated from TET21N cells expressing either control (siControl) or MondoA (siMondoA) siRNAs either with (NT) or without (Doxy) induced N-Myc expression.
2015-01-01 | GSE55538 | GEO
Project description:BACKGROUND: The diabetic macroangiopathy includes coronary heart disease, cerebrovascular disease and peripheral artery disease. Diabetic macroangiopathy is the main cause of death in diabetic patients. The exact pathogenesis of diabetic macroangiopathy is still not completely clear. METHODS: Single-cell transcriptome, spatial transcriptome, and spatial metabolome sequencing were performed on specimens of the anterior tibial artery from 11 amputated patients for visualization and data analysis through bioinformatics. RESULTS: This study reveals the gene-metabolic network in metabolic reprogramming and calcification characteristics in diabetic macrovasculature. Tissue specificity was found in some metabolic pathways. Alpha-linolenic acid metabolism and linoleic acid metabolism were characteristically enriched in the arteriae externa, and folate biosynthesis was characteristically expressed in calcification region. O-glycan biosynthesis, and primary bile acid biosynthesis are enriched in plaques. The calcification area mainly expresses COL1A2 COL6A2 FN1, MIF, SPP1, TNC as ligands to adjust and control media and plaque. The presence of nuclear enrichment related lesion changes around calcification resulted in activation of chemokine function, erk1/2 function and phenylalanine pathway. CONCLUSIONS: This study is the first to construct a spatial gene-metabolic map of complete blood vessels, which provides a basis for the subsequent exploration of the mechanism and clinical transformation of diabetic macrovascular disease.
2024-10-16 | GSE248608 | GEO
Project description:BACKGROUND: The diabetic macroangiopathy includes coronary heart disease, cerebrovascular disease and peripheral artery disease. Diabetic macroangiopathy is the main cause of death in diabetic patients. The exact pathogenesis of diabetic macroangiopathy is still not completely clear. METHODS: Single-cell transcriptome, spatial transcriptome, and spatial metabolome sequencing were performed on specimens of the anterior tibial artery from 11 amputated patients for visualization and data analysis through bioinformatics. RESULTS: This study reveals the gene-metabolic network in metabolic reprogramming and calcification characteristics in diabetic macrovasculature. Tissue specificity was found in some metabolic pathways. Alpha-linolenic acid metabolism and linoleic acid metabolism were characteristically enriched in the arteriae externa, and folate biosynthesis was characteristically expressed in calcification region. O-glycan biosynthesis, and primary bile acid biosynthesis are enriched in plaques. The calcification area mainly expresses COL1A2 COL6A2 FN1, MIF, SPP1, TNC as ligands to adjust and control media and plaque. The presence of nuclear enrichment related lesion changes around calcification resulted in activation of chemokine function, erk1/2 function and phenylalanine pathway. CONCLUSIONS: This study is the first to construct a spatial gene-metabolic map of complete blood vessels, which provides a basis for the subsequent exploration of the mechanism and clinical transformation of diabetic macrovascular disease.
2024-10-16 | GSE248609 | GEO
Project description:Neuroblastoma (NB), a malignant embryonic tumor arising from primitive neural crest cells, accounts for more than 7% of malignancies and around 15% of cancer-related mortality in childhood. Better elucidating the mechanisms of tumorigenesis and aggressiveness is important for improving the therapeutic efficiencies of NB. Through integrated proteomics and validating studies, we discovered that CNBP physically interacted with SMARCC2 in NB cells. To investigate the mechanisms underlying the functions of CNBP and SMARCC2, we employed the Illumina Novaseq 6000 as a discovery platform to analyze the genome-wide occupancy of CNBP and SMARCC2 on target genes in human IMR-32 cells, while the results were further analyzed with CNBP-regulated target genes. The results showed that CNBP repressed the enrichment of SMARCC2 on 124 target genes, especially those involved in ribosome biogenesis, including BYSL, NOP58, and RRP9. Furthermore, we validated the ChIP-seq results by real-time PCR with high identity. Overall, our results provided fundamental information about the genomic enrichment of CNBP and SMARCC2 in human NB cells, and these findings will help us understand the pathogenesis of NB.
2023-08-07 | GSE215795 | GEO