Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma [MYCN_CutAndRun]

ABSTRACT: Current therapies for neuroblastoma are often ineffective and survivors suffer from severe long-term therapy related side-effects, underscoring the need for identification of novel drugging strategies. We performed an in-depth evaluation of phenotypic and molecular responses following exposure of neuroblastoma cells to the rocaglate CR-1-31-B, scrutinizing its mode-of-action through integrative ribosome footprinting and shotgun proteome profiling. We could show that CR-1-31-B significantly reduces tumor growth in vivo without apparent toxicity. By means of combined ribosome footprint and transcriptome analysis we could show that CR-1-31-B treatment induces downregulates factors involved in the G2/M checkpoint, while upregulated targets are enriched for oxidative phosphorylation pathway components and DNA repair. At the proteome level, CR-1-31-B revealed downregulation of a FOXM1 driven gene signature, with TPX2 as prominent marker. Knockdown of TPX2 leads to reduced neuroblastoma cell confluence and elevated levels of DNA damage. In conclusion, our data support CR-1-31-B as a potent novel therapeutic agent in neuroblastoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246722 | GEO | 2026/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma[RNA-Seq]

Project description:Current therapies for neuroblastoma are often ineffective and survivors suffer from severe long-term therapy related side-effects, underscoring the need for identification of novel drugging strategies. We performed an in-depth evaluation of phenotypic and molecular responses following exposure of neuroblastoma cells to the rocaglate CR-1-31-B, scrutinizing its mode-of-action through integrative ribosome footprinting and shotgun proteome profiling. We could show that CR-1-31-B significantly reduces tumor growth in vivo without apparent toxicity. By means of combined ribosome footprint and transcriptome analysis we could show that CR-1-31-B treatment induces downregulates factors involved in the G2/M checkpoint, while upregulated targets are enriched for oxidative phosphorylation pathway components and DNA repair. At the proteome level, CR-1-31-B revealed downregulation of a FOXM1 driven gene signature, with TPX2 as prominent marker. Knockdown of TPX2 leads to reduced neuroblastoma cell confluence and elevated levels of DNA damage. In conclusion, our data support CR-1-31-B as a potent novel therapeutic agent in neuroblastoma.

2026-02-01 | GSE246725 | GEO

TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma

Project description:Current therapies for neuroblastoma, a pediatric tumor arising from immature sympathoblast progenitors of the peripheral sympathetic nervous system, are often ineffective and most survivors suffer from severe long-term therapy related side-effects, underscoring the need for identification of novel drugging strategies with limited toxicity. We performed for the first time an in-depth phenotypic and molecular evaluation of pharmacological eIF4A inhibition in neuroblastoma using the rocaglate CR31B, scrutinizing its mode-of-action through a comprehensive and integrated shotgun proteome profiling and combined ribosome/RNA-seq footprinting approach. Short-term treatment of neuroblastoma cells with CR31B significantly affected viability within the very low nanomolar concentration range. Notably, ribosome footprinting following short-term CR31B exposure (6 hours) revealed amongst others strong enrichment for transcripts encoding proteins involved in N-glycan biosynthesis amongst the downregulated hits, while upregulated targets are enriched for oxidative phosphorylation pathway components. Shotgun proteome profiles during long-term (24h-48h-72h) CR31B exposure revealed a strong enrichment of a FOXM1 driven signature amongst the downregulated hits, a key regulator implicated in cell cycle control and DNA damage response in neuroblastoma. Last, we could show that CR31B significantly reduces tumor growth in vivo without apparent toxicity in a neuroblastoma PDX model. In conclusion, we present CR31B as a potent novel potent therapeutic agent in neuroblastoma.

2026-02-01 | GSE216191 | GEO

TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma

2026-02-01 | GSE216192 | GEO

Ribosome profiling analysis of neuroblastoma cells in response to amidino-rocaglate treatment

Project description:MYCN-amplified neuroblastoma cells exhibit upregulation of translation regulation factors and ribosome biogenesis proteins as a result of MYCN-driven transcriptional amplification. Here, we treated MYCN-amplified and non-amplified neuroblastoma cells with a novel translation inhibitor, amidino-rocaglate CMLD12824, to compare the defects in translational efficiency.

2024-06-25 | GSE261760 | GEO

eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma

Project description:Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with limited treatment options. Although metabolic reprogramming is a hallmark of many cancers, including PDA, previous attempts to target metabolic changes therapeutically have been stymied by drug toxicity and tumour cell plasticity. Here, we show that PDA cells engage an eIF4F-dependent translation program that supports redox and central carbon metabolism. Inhibition of the eIF4F subunit, eIF4A, using the synthetic rocaglate CR-1-31-B (CR-31) reduced the viability of PDA organoids relative to their normal counterparts. In vivo, CR-31 suppresses tumour growth and extends survival of genetically-engineered murine models of PDA. Surprisingly, inhibition of eIF4A also induces glutamine reductive carboxylation. As a consequence, combined targeting of eIF4A and glutaminase activity more effectively inhibits PDA cell growth both in vitro and in vivo. Overall, our work demonstrates the importance of eIF4A in translational control of pancreatic tumour metabolism and as a therapeutic target against PDA.

2019-10-03 | GSE125380 | GEO

RNA-seq to investigate gene expression profiles in tumor infiltrating CD8+ T cells with TPX2-overexpression

Project description:CD8+ T cells were isolated from fresh human HCC tissues, then treated with lentivirus for TPX2 over-expression or control

2024-02-15 | E-MTAB-10040 | biostudies-arrayexpress

TPX2 Amplification-Driven Aberrant Mitosis in Long-Term Cultured Human Embryonic Stem Cells

Project description:Although human embryonic stem cells (hESCs) are equipped with highly effective machinery for the maintenance of genome integrity, the frequency of genetic aberrations during long-term in vitro hESC culture has been a serious issue that raises concerns over their safety in future clinical applications. By passaging hESCs over a broad range of timepoints, we found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in the late-passaged hESCs (LP-hESCs) in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs). Through high-resolution genome-wide approaches and by following transcriptome analysis, we found that LP-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2 (targeting protein for Xklp2), a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stability, misaligned chromosomes, and polyploidy. This data suggests that the amplification and increased transcription of the TPX2 gene at 20q11.21 could contribute to an increase in aberrant mitosis due to altered spindle dynamics.

2021-02-26 | GSE167495 | GEO

Ribosome profiling analysis of neuroblastoma cells in response to amidino-rocaglate treatment

Project description:Ribosome profiling analysis of neuroblastoma cells in response to amidino-rocaglate treatment

| PRJNA1088608 | ENA

TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma

Project description:TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma

| PRJNA892531 | ENA

TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma

Project description:TPX2 as key downstream target of the eIF4A controlled translational program in MYCN driven neuroblastoma

| PRJNA892548 | ENA