Gene expression profile of human neuroblastoma cell line SHSY-5Y after LMO1 knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE130747 | GEO | 2019/11/10
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression profile of human neuroblastoma cell line SHSY-5Y after LMO1 knockdown
| PRJNA541271 | ENA
Project description:High levels of LMO1 expression synergizes with MYCN to accelerate neuroblastomagenesis, enhance disease penetrance and promote widespread metastasis in zebrafish. Transcriptomic analysis of human neuroblasotma cells with programed expression of LMO1 vs vector control or neuroblastoma cells with differential endogenous LMO1 expression revealed that gene signitures affecting tumor cell-extracellular matrix interaction are significantly associated with high levels of LMO1 expression. Our findings provide compelling evidence for a major pathogenic role of LMO1 in MYCN-driven neuroblastoma.
2017-07-31 | GSE90087 | GEO
Project description:Neuroblastoma is an embryonal tumor of the peripheral sympathetic nervous system. Elevated expression of the transcription factor LMO1 and the polymorphisms within this gene are associated with the susceptibility to develop neuroblastoma. LMO1 has been implicated as an oncogene in T-cell acute lymphoblastic leukemia; however, the transcriptional targets regulated by this protein in neuroblastoma cells are unknown. Here, we identify the genes and molecular pathways controlled by LMO1 in neuroblastoma cells. ChIP-seq analysis revealed that LMO1-bound regions are frequently co-occupied by GATA3 and MYCN proteins and are associated with active histone marks in neuroblastoma cells. RNA-seq analysis demonstrated that LMO1 regulates gene expression in a tumor type-specific manner. One high-confidence target gene directly regulated by LMO1 and MYCN is ASCL1, which is more highly expressed in adrenergic subtype of neuroblastoma cells as compared to normal neuronal cells. High levels of ASCL1 expression are associated with inferior overall survival in primary human neuroblastoma cases. ChIP-seq analysis identified a regulatory element controlling ASCL1 expression that is bound by LMO1, MYCN and the members of the core regulatory circuitry in neuroblastoma cells. Furthermore, ASCL1 is required for neuroblastoma cell growth and regulates genes responsible for repression of neuronal cell differentiation. Taken together, our results implicate ASCL1 as a critical downstream target of LMO1 in the molecular pathogenesis of neuroblastoma.
2019-11-09 | GSE120074 | GEO
Project description:RNA-seq analysis was performed in Kelly neuroblastoma cell line to analyze gene expression changes after LMO1 or MYCN knockdown.
2019-11-10 | GSE118823 | GEO
Project description:A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility in children and oncogenic addiction to LMO1 in the tumor cells1. Here we sought to discover the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation, and transcription factor binding sites. SNP rs2168101 G>T was the most highly associated variant (combined P=7.47x10-29, Odds Ratio 0.65, 95% CI: 0.60-0.70) and resided in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumor formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P=0.028) in neuroblastoma primary tumors and ablates GATA3 binding (P=0.007). We demonstrate monoallelic LMO1 expression from the G-containing strand in tumors heterozygous for this SNP as demonstrated both by RNA sequencing (P<0.0001) and reporter assays (P=0.002). These findings show that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumor cells.
2015-10-18 | GSE65664 | GEO
Project description:The SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1. Gene expression profiles of thymocytes from SCL-LMO1 transgenic and age-matched non transgenic Cd3ε-/- mice were compared to identify candidate genes that confer self-renewal capability to pre-leukemic thymocytes.
2015-11-05 | E-GEOD-74659 | biostudies-arrayexpress
Project description:To elucidate potential role of piRNAs in Neuroblastoma (NB), we performed the genome wide profiling in two human NB cell lines, IMR-32 and SH-SY-5Y by adopting high-throughput RNA sequencing (RNA-Seq) and unveil their possible functions in neoplastic pathways. The RNA sequencing results revealed both known and novel piRNAs in both the cell lines. We observed a total 630 annotated mature piRNAs, distributed across chromosomes and mitochondria which were mapped to various genomic locations such as introns, protein coding regions, repeats, pseudogenes, ncRNAs etc. This is the first study reporting the extensive catalogue of human NB piRNAs which will provide a useful resource to dissect complex neoplastic events that are possibly mediated by piRNAs in neuroblastoma. Moreover, these piRNAs could be used as probable small RNA biomarkers for the Neuroblastoma.
2018-03-20 | GSE83945 | GEO
Project description:The trace element manganese is essential for normal development for all the organisms. Overexposure of manganese may leads to multiple neuronal disorders such as Parkinson, manganism. To explore the molecular mechanism of manganese induced neurotoxicity, gene expression profiling was performed on human neuroblastoma SHSY-5Y cells. Cells were exposed to sub-lethal concentration of manganese (100 μM) for 24 hrs. Our result demonstrates that manganese alter multiple biological pathways including chromatin assembly, neurogenesis and apoptotic pathways.Cells grown in 75mm2 flask. three replicates for each sample
2016-07-01 | GSE70845 | GEO
Project description:The trace element manganese is essential for normal development for all the organisms. Overexposure of manganese may leads to multiple neuronal disorders such as Parkinson, manganism. To explore the molecular mechanism of manganese induced neurotoxicity, gene expression profiling was performed on human neuroblastoma SHSY-5Y cells. Cells were exposed to sub-lethal concentration of manganese (100 μM) for 24 hrs. Our result demonstrates that manganese alter multiple biological pathways including chromatin assembly, neurogenesis and apoptotic pathways.Cells grown in 75mm2 flask. three replicates for each sample SHSY5Y cells grown in MEM:F12 media (1:1) were treated with manganese and total RNA was isolated from cells after 24 hour exposure Three replicate were used for the experiment
2016-07-01 | E-GEOD-70845 | biostudies-arrayexpress
Project description:Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like “mesenchymal” cell state and a more differentiated sympathetic “adrenergic” cell state. These cell states are governed by autoregulatory transcriptional loops called core regulatory circuitries (CRCs), which drive the early development of sympathetic neuronal progenitors from migratory neural crest cells during embryogenesis. The adrenergic cell identity of neuroblastoma requires LMO1 as a transcriptional co-factor. Both LMO1 expression levels and the risk of developing neuroblastoma in children are associated with a single nucleotide polymorphism G/T that affects a GATA motif in the first intron of LMO1. Here we showed that wild-type zebrafish with the GATA genotype developed adrenergic neuroblastoma, while knock-in of the protective TATA allele at this locus reduced the penetrance of MYCN-driven tumors, which were restricted to the mesenchymal cell state. Whole genome sequencing of childhood neuroblastomas demonstrated that TATA/TATA tumors also exhibited a mesenchymal cell state and were low risk at diagnosis. Thus, conversion of the regulatory GATA to a TATA allele in the first intron of LMO1 reduced the neuroblastoma initiation rate by preventing formation of the adrenergic cell state, a mechanism that was conserved over 400 million years of evolution separating zebrafish and humans.
2023-04-25 | GSE224158 | GEO