Neuroblastoma: MYCN normal vs. MYCN amplified
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53371 | GEO | 2013/12/17
SECONDARY ACCESSION(S): PRJNA231852
REPOSITORIES: GEO
Similar Datasets
Project description:To evaluate the expression of genes associated with MYCN in NB, 10 tumors with MYCN amplification and 10 with normal MYCN copy number were subjected to oligonucleotide microarray using Agilent oligo microarray chips. Two-condition experiment, MYCN normal vs. MYCN amplified 10 NB patient tissues for each group.
2013-12-17 | E-GEOD-53371 | biostudies-arrayexpress
Project description:MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) that predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to aggressiveness in MNA+ NB remains poorly understood. Here we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently co-expressed with MYCN, and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN in MNA+ NB, among which we uncover Myosin 1B (MYO1B) as being highly expressed in MNA+ NB. MYO1B promotes aggressive features, including invasive capacity in vitro, as well as extravasation and distant metastasis in vivo. Global secretome and proteome profiling further delineate MYO1B as a major regulator of secretome reprogramming in MNA+ NB cells. Moreover, we identify the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism that promotes the aggressiveness of MNA+ NB, and independently of MYCN. Furthermore, we find that MYO1B is upregulated in association with other oncoproteins during cellular transformation, and is dramatically increased in multiple human cancer types, suggesting a crucial role of MYO1B in cancers in addition to MNA+ NB.
2023-10-24 | PXD039410 | Pride
Project description:The MYCN locus is amplified in about half of high-risk neuroblastoma tumors. To identify genomic loci occupied by MYCN protein in the MYCN-amplified neuroblastoma cell lines NGP, Kelly and NB-1643, we performed chromatin immunoprecipitation coupled with Next-Generation Sequencing (ChIP-seq) using an anti-MYCN antibody.
2017-08-02 | GSE94782 | GEO
Project description:MYCN amplification in neuroblastoma leads to aberrant expression of MYCN oncoprotein, which binds active genes promoting transcriptional amplification. Yet how MYCN coordinates transcription elongation to meet productive transcriptional amplification and which elongation machinery represents MYCN-driven vulnerability remain to be identified. We conducted a targeted screen of transcription elongation factors and identified the super elongation complex (SEC) as a unique vulnerability in MYCN-amplified neuroblastomas. MYCN directly binds EAF1 and recruits SEC to enhance processive transcription elongation. Depletion of EAF1 or AFF1/AFF4, another core subunit of SEC, leads to a global reduction in transcription elongation and elicits selective apoptosis of MYCN-amplified neuroblastoma cells. A combination screen reveals SEC inhibition synergistically potentiates the therapeutic efficacies of FDA-approved BCL2 antagonist ABT-199, in part due to suppression of MCL1 expression, both in MYCN-amplified neuroblastoma cells and in patient-derived xenografts. These findings identify disruption of the MYCN-SEC regulatory axis as a promising therapeutic strategy in neuroblastoma.
2023-05-10 | PXD039332 | Pride
Project description:To identify the MYCN transcription factor binding sites across the genome, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MYCN and anti-IgG antibodies on a MYCN-amplified NB cell line, SK-N-BE(2)-C. Identification of MYCN binding in neuroblastoma cells.
2016-05-16 | E-GEOD-72640 | biostudies-arrayexpress
Project description:Polycomb-group complexes are evolutionarily conserved epigenetic machineries that regulate stem cell fate decisions/development and are also implicated in tumorigenesis mainly by histone modification. PRC1 complexes mediates ubiquitylation of histone H2A on lysine 119 and consists of PRC1.1 to PRC1.6 complexes. Here, we studied the functional roles of a PRC1.6 molecule L3MBTL2 in neuroblastoma (NB) cells. L3MBTL2 knockout- and knockdown-experiments elucidated that L3MBTL2 depletion suppressed NB cell proliferation according with cell cycle arrest and gamma-H2A up-regulation. L3MBTL2 knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis detected the suppressed cell cycle-related pathways and the activated the differentiation-related pathways. The remarkable de-repressed genes by the L3MBTL2 knockout were BRME1 and NRIP3. ChIP experiments showed co-localization of the PRC1.6 components PCGF6/E2F6/L3MBTL2 and MYCN at the transcription start sites (TSS) of these genes. L3MBTL2 knockout reduced H2AK119ub marks at the TSS regions but PCGF6 binding was heterogeneously changed. This study clarified the significance of PRC1.6 molecule L3MBTL2 in NB cell homeostasis and the epigenetic mechanism of the L3MBTL2-mediated gene suppression in NB that regulates the PRC1.6 complex localization and H2AK119 mono-ubiquitination in a gene locus-specific manner.
2023-09-26 | GSE201512 | GEO
Project description:Neuroblastoma (NB) is an embryonal tumor with various clinical presentations and behaviors. Several genomic alterations has been well-studied in NB, among which genomic amplification of MYCN oncogene, is a strong prognostic biomarker with worsens outcome. Long noncoding RNAs (lncRNAs), constitute major proportion of the cellular transcripts with no coding capacity. One of their function is to guide transcription factors to the target genes and facilitate gene expression. However, relative contribution of lncRNA and MYCN to the advanced NB has remained unclear. Herein, by applying a network-based integrative analysis on MYCN amplified and MYCN nonamplified lncRNA expression profile from both RNA-seq and microarray platform, we identified lncRNA, SNHG1 to be differentially expressed and strongly correlated with MYCN in MYCN-amplified NB. The expression of SNHG1 was validated by RT-qPCR in NB cell lines. Survival analysis revealed that higher expression of SNHG1 significantly associates with poor patient survival. Moreover, knockdown of MYCN in MYCN-amplified NB cell lines inhibited SNHG1 expression. Furthermore, to unravel the role of SNHG1 in NB, we extracted SNHG1-interacting proteins by RNA-protein pull down assay coupled with doi:10.6342/NTU201701980 ! ! VI liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 27 SNHG1-interacting proteins in common from three NB cell lines. However, only three SNHG1-interacting proteins, MATR3, YBX1 and HHRNPL have binding site detected by DeepBind motif analysis. Western blot confirms interaction of MATR3 with SNHG1. Additionally, we further validated the direct interaction between MATR3 and SNHG1 by RNA-immunoprecipation (IP). MATR3 is known to be involved in RNA transport and stabilization. Therefore, we proposed that MATR3 after interacting with SNHG1 might help in SNHG1 transcription and stabilization. In conclusion, our study unveils that SNHG1 could be a prognostic marker for high-risk NB and possibly stabilized by MATR3. Our results might provide future directions for the development of therapeutic strategies against high-risk NB.
2022-03-01 | PXD007121 | Pride
Project description:Neuroblastoma (NB), the most common extracranial solid tumor in children, often metastasizes at a high rate. Here, we demonstrate that loss of function of the growth arrest-specific 7 gene (GAS7), located on Chr17p13.1, a deleted region in a subset of high-risk NB, accelerates dissemination of MYCN-overexpressing tumor cells in both zebrafish and xenografted mice models. Transcriptomic analysis of neuroblasotma tumors isolated from transgenic zebrafish overexpressing MYCN oncogene alone or MYCN with knockout of gas7 gene revealed that gene signitures affecting tumor cell-cell or cell-extracellular matrix interactions are significantly downregulated in tumors with gas7 loss of function. Our results provide the first genetic evidence that loss of function of a gene located in the Chr17p region contributes significantly to NB metastasis.
2021-02-04 | GSE131307 | GEO
Project description:To identify the MYCN transcription factor binding sites across the genome, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MYCN and anti-IgG antibodies on a MYCN-amplified NB cell line, SK-N-BE(2)-C.
2016-05-16 | GSE72640 | GEO
Project description:Gene expression is regulated by promoters and enhancers marked by histone H3-lysine-27 acetylation (H3K27ac), which is established by the paralogous histone acetyltransferases (HATs), EP300 and CBP. These enzymes display overlapping regulatory roles in untransformed cells, but less characterized roles in cancer cells. We demonstrate that the majority of high-risk pediatric neuroblastomas (NB) depend on EP300, whereas CBP has a limited role. EP300 controls enhancer acetylation by interacting with TFAP2?, a transcription factor member of the lineage-defining transcriptional core regulatory circuitry (CRC) in NB. To disrupt EP300, we developed a proteolysis-targeted-chimaera (PROTAC) compound termed ?JQAD1? that selectively targets EP300 for degradation. JQAD1 treatment causes loss of H3K27ac at CRC enhancers and neuroblastoma apoptosis, with limited toxicity to untransformed cells where CBP compensates. Comparing HAT inhibition and EP300-specific degradation, we identified a non-catalytic role for EP300 in promoting MYCN expression and repression of apoptosis.
2021-11-09 | GSE159615 | GEO