Transcriptome changes after NEN treament in neuroblastoma cell
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE209801 | GEO | 2022/10/26
REPOSITORIES: GEO
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Project description:Genome wide DNA methylation profiling of neuroblastoma cell SK-N-BE(2) treated by 1µM NEN under normoxia and hypoxia for 24hrs. The IInfinium Human MethylationEPIC BeadChip v1.0 B5 was used to obtain DNA methylation profiles across approximately 850,000 methylation sites in the genome of neuroblastoma. Samples included 4 group with 3 biological replicates: (1) normoxia_CTRL (2) normoxia_NEN (3) hypoxia_CTRL (4) hypoxia_NEN
2022-10-26 | GSE211558 | GEO
Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with diverse clinical behaviors. Even with multimodal therapies, high-risk neuroblastoma has an unfavorable outcome irrespective of MYCN amplification, a well-established oncogenic driver in neuroblastoma pathogenesis, and its genetic heterogeneity has largely impeded efforts to correlate molecular targets with biological consequences for more effective treatment strategies. Here, using a gene expression-based approach, we identified the FDA-approved anthelmintic niclosamide as a potential anti-neuroblastoma drug. By combining the gene expression signature associated with high-risk neuroblastoma and the recurrent drug−transcript relationships inferred from up to one million perturbational gene expression profiles, our algorithm predicted effective therapeutic candidates by evaluating the extent to which a given compound or their combinations could ‘reverse’ the high-risk signature. Furthermore, we performed quantitative polymerase chain reaction (qPCR) to validate top five candidate reverse genes which are involved in DNA replication, including cyclin A2 (CCNA2), minichromosome maintenance 10 replication initiation factor (MCM10), ERCC excision repair 6 like, spindle assembly checkpoint helicase (ERCC6L), kinesin family member 20A (KIF20A), and RuvB like AAA ATPase 1 (RUVBL1). Indeed, those five genes were downregulated in niclosamide-treated cells, indicating niclosamide suppressed DNA replication and then inhibited cell proliferation. Using cell proliferation and clonogenic assays as well as flow cytometry, we determined the cytotoxic effects of niclosamide in MYCN-amplified SK-N-DZ and non-amplified SK-N-AS cells. The results showed that niclosamide could effectively reduce not only cell proliferation and colony formation but also trigger cell cycle arrest and apoptosis. Moreover, we conducted human tumor xenografts in a nude mice model to evaluate the in vivo efficacy of niclosamide and found that it significantly suppressed tumor growth and prolonged survival rate, but doesn’t cause organ damage and change body weight. To explore the molecular mechanism of niclosamide, stable-isotope dimethyl labeling strategy for quantitative proteomics was performed on both cell-based or xenograft-based MYCN-amplified SK-N-DZ and MYCN-nonamplified SK-N-AS models. We confirmed niclosamide not only mediated the function of mitochondrial electron transport chain but also the other functions in high risk neuroblastoma cell lines and xenografts. The results suggest that our developed expression-based strategy is useful for drug discovery and provides the possibility of repurposing the anthelminthic drug niclosamide for treating high-risk neuroblastoma therapy.
2022-02-23 | PXD010745 | Pride
Project description:Transcriptome changes after NEN treament in neuroblastoma cell
| PRJNA862500 | ENA
Project description:Hepatocellular carcinoma (HCC) is a fatal malignancy with a dismal prognosis. The recent advances in genomics and transcriptomics have led to large volumes of molecular data for HCC, providing an unprecedented opportunity to translate these data into more effective therapeutics. By creating HCC gene expression signatures and comparing with drug response signatures from multiple datasets, we identified four antihelminthics (from over 1000 FDA-approved drugs) that can reverse the HCC disease gene expression. Among these four, niclosamide was the top hit, which we further evaluated in clinically relevant HCC cell lines and patient-derived xenografts (PDX). Given the poor water-solubility and limited systemic bioavailability of niclosamide, we also evaluated its ethanolamine salt (NEN), which has improved solubility and bioavailability. Both niclosamide and NEN significantly inhibited HCC cell proliferation in vitro, which was associated with down-regulation of key proteins involved in the AKT-mTOR, Wnt, Stat3, and EGFR/Ras/Raf signaling pathways. NEN additionally decreased the growth of three PDX models after oral administration (1,5000 ppm in food) for 4-6 weeks. Expression profiling demonstrated that niclosamide and NEN induced highly similar gene expression changes in HepG2 cells and in PDX models, and that both compounds significantly reversed HCC gene expression in vitro and in vivo . Our results suggest that NEN may be a preferred drug candidate for the treatment of HCC.
2017-03-01 | GSE77322 | GEO
Project description:Neuroblastoma is a solid pediatric tumor with heterogeneous clinical behaviors. Chemotherapy is widely used to treat neuroblastoma. However, dose-dependent responses and chemoresistance mechanisms of neuroblastoma cells to anticancer drugs remain challenges in various conditions. Here, we investigated the dose-dependent effects of topotecan on human neuroblastoma cells (SK-N-SH, SH-SY5Y, and SK-N-BE) under various nutrient supply conditions. Serum-starved human neuroblastoma cells showed reduced toxicity, and their survival rate increased upon treatment with a high concentration (1 μM) of topotecan. Quantitative profiling of global and phosphoproteome identified 12,959 proteins and 48,812 phosphosites, respectively, from SK-N-SH cells. Network analysis revealed that topotecan up-regulated DNA repair and cholesterol-mediated topotecan efflux, resulting in topotecan resistance. Results of DNA damage assay, cell cycle, and quantitative analyses of membrane cholesterol supported the validity of these resistance factors and their applicability to all neuroblastoma cells investigated in this study. Our results provide a model for high dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.
2021-03-25 | PXD014648 | Pride
Project description:Neuroblastoma cell lines SK-N-AS(-TRAIL) and SH-SY5Y were xenografted in mice to study them in vivo
2021-10-01 | GSE125058 | GEO
Project description:We report a previously unrecognized role of IRF2BP2 in neuroblastoma. To explore IRF2BP2-dependent gene regulation, RNA-seq analysis was conducted and the differently expressed genes were revealed in the IRF2BP2-knockdown SK-N-BE(2) cells in comparison to control group. We find that IRF2BP2 contributes to maintenance ADRN signature of neuroblastoma cell.
2024-06-24 | GSE236390 | GEO
Project description:Following treatment with the de-methylating agent 5-aza-deoxycytidine (DAC), the gene expression profiles of neuroblastoma cell lines Kelly, SK-N-AS and NGP were analysed in order to examine the relationship between transcriptional re-activation and promoter region DNA methylation.<br>In addition, the neuroblastoma cell line SK-N-BE was treated with all-trans-retinoic acid (ATRA) in order to examine the impact this differentiation agent has on DNA methylation status.
2010-11-03 | E-MEXP-2557 | biostudies-arrayexpress
Project description:We studied transcriptional changes by Illumina HumanHT-12 v4 microarrays in 2 Neuroblastoma cell lines after i-BET-726 treatment 2 neuroblastoma cell lines SK-N-SH and CHP-212 were treated with i-BET-726 at 100nM or 1uM concentrations for 16 hrs to study gene expression.
2013-08-23 | E-GEOD-47386 | biostudies-arrayexpress
Project description:Single-color gene expression profiles from 3 neuroblastoma cell lines were generated using 44K oligonucleotide microarrays. To gain insights into the molecular processes occurring upon FOXP1 re-expression, we performed series of time-resolved gene expression measurements in FOXP1 and GFP transgenic neuroblastoma cell lines. Single-color gene expression profiles from 3 neuroblastoma cell lines were generated using 44K oligonucleotide microarrays. Total RNA of FOXP1- and GFP-expressing IMR-32, CHP-212 and SK-N-BE(2) cells was isolated at 0, 12, 24 and 72 h using Trizol. To determine global differences in the expression profiles of FOXP1- and GFP-induced IMR-32, CHP-212 and SK-N-BE(2) cells, mean expression levels of each gene between FOXP1-induced and control (GFP) cells were compared.
2014-10-17 | E-GEOD-62419 | biostudies-arrayexpress