Single-cell sequencing of neuroblastoma CHP134 cells treated with doxazosin, isotretinoin (13cRA) and their combination.
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ABSTRACT:
PROVIDER: PRJNA972457 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24548571_1.fastq.gz | Fastqsanger.gz | |||
| SRR24548571_2.fastq.gz | Fastqsanger.gz | |||
| SRR24548572_1.fastq.gz | Fastqsanger.gz | |||
| SRR24548572_2.fastq.gz | Fastqsanger.gz | |||
| SRR24548573_1.fastq.gz | Fastqsanger.gz |
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Project description:Neuroblastoma (NB) is an aggressive childhood tumor, with high-risk cases having a 5-year overall survival probability of about 50%. The multimodal therapeutic scheme of NB includes isotretinoin (13cRA), used in the post-consolidation phase as an anti-proliferative and pro-differentiative agent to minimize residual disease and prevent relapse. Administration of doxazosin, a safe α1-antagonist used in pediatric patients, with 13cRA in NB xenografted mice exerted a marked control of tumor growth, while each of the two drugs alone was ineffective. To unveil the molecular mechanisms underlying this synergism, single-cell RNA-seq was performed in CHP134 control cells, and cells treated with 13cRA (5 uM), doxazosin (10 uM), and their combination. The data revealed that the transcriptome of single cells was markedly reprogrammed when exposed to 13cRA and to the combination of doxazosin and 13cRA, but not when exposed to doxazosin alone. In detail, we identified 91 genes as specific markers of 307 cells treated with the drug combination: 41 synergistically downregulated and 50 upregulated. Functional analysis of these synergistically expressed genes reported significant enrichment of genes related to apoptosis, control of the cell cycle, and neuronal identity. We, therefore, preclinically identify the α1B adrenergic receptor as a novel pharmacological target in NB. We propose evaluating the addition of α1-antagonists in the post-consolidation therapy of NB to more efficiently control residual disease. Keywords: isotretinoin, 13cRA, 13-cis retinoic acid, doxazosin, neuroblastoma,single-cell RNA-seq, iCELL8, adrenergic receptors, α-blockers, combinatorial therapy, synergy
2023-05-29 | GSE232498 | GEO
Project description:Translatome profiling of neuroblastoma cells CHP134 treated with isotretinoin (13cRA), isorhamnetin (ISR), and their combination
| PRJNA971903 | ENA
Project description:Neuroblastoma (NB) is an aggressive childhood tumor, with high-risk cases having a 5-year overall survival probability of about 50%. The multimodal therapeutic scheme of NB includes isotretinoin (13cRA), used in the post-consolidation phase as an anti-proliferative and pro-differentiative agent to minimize residual disease and prevent relapse. Through a small molecule screening, we identified isorhamnetin (ISR) as a synergistic compound with 13cRA in inhibiting up to 80% of NB cell viability. To unveil the molecular mechanisms underlying this synergism, microarray analysis was performed in CHP134 control cells, and cells treated with 13cRA (5uM), ISR (15uM), and their combination. This analysis revealed that 13cRA ISR synergism is accompanied by a marked increase in the expression of the adrenergic receptor α1B (ADRA1B) gene. Administration of doxazosin, a safe α1-antagonist used in pediatric patients, with 13cRA in NB xenografted mice exerted a marked control of tumor growth, while each of the two drugs alone was ineffective. We, therefore, preclinically identify the α1B adrenergic receptor as a novel pharmacological target in NB. We propose evaluating the addition of α1-antagonists in the post-consolidation therapy of NB to more efficiently control residual disease. Keywords: isotretinoin, 13cRA, 13-cis retinoic acid, isorhamnetin, ISR, neuroblastoma, polysome profiling, translatome, adrenergic receptors, α-blockers, combinatorial therapy, synergy
2023-05-29 | GSE232388 | GEO
Project description:This study was undertaken to assess transcriptional and epigenetic heterogeneity a the level of individual cells within neuroblastoma cell lines, and to compare cell lines with MYCN amplificaion to cell lines without MYCN amplification. Methods: We used 10X Genomics multiome sequencing technology to perform joint gene expression and ATAC profiling on thousands of nuclei isolated from the following human neuoblastoma cell lines: SHSY5Y, SK-N-AS, SK-N-SH, SK-N-DZ, Be-2c, and CHP134. Results: We found considerable gene expression and epigeneic heterogeneity both within and between neuroblastoma cell lines. Conclusion: Joint single-nucleus RNA sequencing and single-nucleus ATAC sequencing has demonsrated that neuroblastoma cell lines are heterogeneous, which may have implications for therapeutic strategies.
2024-09-17 | GSE262189 | GEO
Project description:Neuroblastoma (NB) is the most frequent extracranial solid tumour of childhood. Clinical courses are highly variable, ranging from spontaneous regression/maturation to rapid progression despite intensive multimodal therapy. The estimation of 5-year event free survival in high-risk patients of only about 40 % stresses an importance of novel therapeutic strategies. A number of iron chelators have demonstrated marked in vitro and in vivo anti-tumor activity and are currently being developed as novel anti-cancer agents. Therefore, the potential antitumor effect of iron chelators in NB cancer was investigated. Among the compounds tested, ciclopirox olamine (CPX) was shown to be one of the most effective intracellular iron chelators in NB cells. To unveil the molecular mechanisms underlying the effects of CPX on viability of NB cells, microarray analysis was performed in CHP134 control cells and cells treated with 5 M-BM-5M CPX for 90 minutes. Inclusion of both total RNA (reflecting transcriptional status of the cells) and polysomal RNA (approximating the proteomic representation of the cells) provided us with a deeper understanding of changes in the cells upon CPX treatment. Keywords: ciclopirox olamine, iron chelator, neuroblastoma, translatome profiling, transcriptome profiling. Keywords: ciclopirox olamine, iron chelator, neuroblastoma, translatome profiling, transcriptome profiling, polysomal profiling, polysomal RNA, translational control, translational profiling, polysome profiling Microarray analysis was performed to enable a comprehensive view of the changes in the transcriptional and translational status of the cells in response to the treatment with an iron chelator CPX. Polysomal RNA and total RNA were isolated from vehicle-treated CHP134 cells and CHP134 cells treated with 5 M-BM-5M CPX for 90 minutes. Each condition is represented by three biological replicates, i.e. the experiment was repeated starting each time from cells seeding yielding an independent RNA sample. In total, 12 samples corresponding to 4 conditions were subjected to microarray analysis.
2015-02-04 | E-GEOD-60675 | biostudies-arrayexpress
Project description:Neuroblastoma (NB) is the most frequent extracranial solid tumour of childhood. Clinical courses are highly variable, ranging from spontaneous regression/maturation to rapid progression despite intensive multimodal therapy. The estimation of 5-year event free survival in high-risk patients of only about 40 % stresses an importance of novel therapeutic strategies. A number of iron chelators have demonstrated marked in vitro and in vivo anti-tumor activity and are currently being developed as novel anti-cancer agents. Therefore, the potential antitumor effect of iron chelators in NB cancer was investigated. Among the compounds tested, ciclopirox olamine (CPX) was shown to be one of the most effective intracellular iron chelators in NB cells. To unveil the molecular mechanisms underlying the effects of CPX on viability of NB cells, microarray analysis was performed in CHP134 control cells and cells treated with 5 µM CPX for 24 hours. Inclusion of both total RNA (reflecting transcriptional status of the cells) and polysomal RNA (approximating the proteomic representation of the cells) provided us with a deeper understanding of changes in the cells upon CPX treatment. Keywords: ciclopirox olamine, iron chelator, neuroblastoma, translatome profiling, transcriptome profiling, polysomal profiling, polysomal RNA, translational control, translational profiling, polysome profiling Microarray analysis was performed to enable a comprehensive view of the changes in the transcriptional and translational status of the cells in response to the treatment with an iron chelator CPX. Polysomal RNA and total RNA were isolated from vehicle-treated CHP134 cells and CHP134 cells treated with 5 µM CPX for 24 hours. Each condition is represented by three biological replicates, i.e. the experiment was repeated starting each time from cells seeding yielding an independent RNA sample. In total, 12 samples corresponding to 4 conditions were subjected to microarray analysis.
2016-06-01 | E-GEOD-53187 | biostudies-arrayexpress
Project description:The impact of drugs inhibiting DNA methylation (5-aza-2'-deoxycytodine, DAC) and EZH2 (EPZ-6438) on the neuroblastoma transcriptome was analyzed in two neuroblastoma cell lines. Parallel analyses investigated associated changes in histone modification and DNA methylation. The neuroblastoma cell lines Be(2)-C and IMR5-75 were treated with DAC and EPZ-6438 in combination or alone. Controls were treated with solvent (DMSO). RNA was isolated and sequenced.
2016-09-08 | E-GEOD-79859 | biostudies-arrayexpress
Project description:The impact of drugs inhibiting DNA methylation (5-aza-2'-deoxycytodine, DAC) and EZH2 (EPZ-6438) on the neuroblastoma methylome was analyzed in two neuroblastoma cell lines. Parallel analyses investigated associated changes in histone modification and RNA expression. The neuroblastoma cell lines Be(2)-C and IMR5-75 were treated with a combination of DAC and EPZ-6438. Controls were treated with solvent (DMSO). DNA was isolated, bisulphite converted and hybridised to the llumina HumanMethylation450 BeadChip
2016-09-08 | E-GEOD-80243 | biostudies-arrayexpress
Project description:RNA-seq upon JQ1 (1 uM), THZ1 (35 nM), UT (untreated) or combination treatment in the neuroblastoma cell line IMR-5/75. Analysis was performed 10h upon treament. Four biological replicates per condition.
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Project description:The CDK7 inhibitor THZ1 has been shown to suppress MYCN gene transcription but not cause significant cell death as a single agent. The tyrosine kinase inhibitors (TKIs) ponatinib and lapatinib were found to exert synergistic anti-cancer effects in combination with the CDK7 inhibitor THZ1, on MYCN amplified neuroblastoma cell lines.
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