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

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: GSE246725 | GEO | 2026/02/01

REPOSITORIES: GEO

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

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