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GEO accession GSE216193 is currently private and is scheduled to be released on Mar 01, 2024.

ABSTRACT: GEO accession GSE216193 is currently private and is scheduled to be released on Mar 01, 2024.

PROVIDER: PRJNA892531 | ENA |

REPOSITORIES: ENA

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

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

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

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.

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

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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

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2026-02-01 | GSE216193 | GEO

Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor

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