Cherkaoui et al. 2024 (PRJNA1022492)

General Details

Title Combined Dietary and Pharmacological Depletion of Polyamines Targets Oncogenic Translation in Neuroblastoma
Organism
Number of Samples 20
Release Date 2023/09/29 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP463937
ENA SRP463937
GEO GSE244378
BioProject PRJNA1022492

Publication

Title
Authors Cherkaoui S, Yang L, McBride M, Turn CS, Lu W, Eigenmann C, Allen GE, Panasenko OO, Zhang L, Vu A, Liu K, Li Y, Gandhi OH, Surrey L, Wierer M, White E, Rabinowitz JD, Hogarty MD, Morscher RJ
Journal bioRxiv : the preprint server for biology
Publication Date 2024 Jan 8
Abstract Neuroblastoma is a highly lethal childhood tumor derived from differentiation-arrested neural crest cells 1,2 . Like all cancers, its growth is fueled by metabolites obtained from either circulation or local biosynthesis 3,4 . Neuroblastomas depend on local polyamine biosynthesis, with the inhibitor difluoromethylornithine showing clinical activity 5 . Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumor differentiation, and profound survival gains in the TH- MYCN mouse model. Specifically, an arginine/proline-free diet decreases the polyamine precursor ornithine and augments tumor polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at adenosine-ending codons. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by the diet-drug combination, favors a pro-differentiation proteome. These results suggest that the genes of specific cellular programs have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of pediatric cancers.
PMC PMC10802427
PMID 38260457
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR26226446 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226445 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226444 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226443 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226442 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226441 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226440 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226439 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226438 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226437 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226436 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226435 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226434 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226433 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226432 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226431 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226430 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226423 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226422 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
SRR26226421 PRJNA1022492 Mus musculus Neuroblast Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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