A multi-omics approach reveals enrichment in metabolites involved in the regulation of the glutathione pathway in LIN28B-dependent cancer cells.

ABSTRACT: The RNA-binding protein LIN28B, identified as an independent risk factor in high-risk neuroblastoma patients, is implicated in adverse treatment outcomes linked to metastasis and chemoresistance. Despite its clinical significance, the impact of LIN28B on neuroblastoma cell metabolism remains unexplored. This study employs a multi-omics approach, integrating transcriptome and metabolome data, to elucidate the global metabolic program associated with varying LIN28B expression levels over time. Our findings reveal that escalating LIN28B expression induces a significant metabolic rewiring in neuroblastoma cells. Specifically, LIN28B prompts a time-dependent increase in the release rate of metabolites related to glutathione and aminoacyl-tRNA biosynthetic pathways, concomitant with a reduction in glucose uptake. These results underscore the pivotal role of LIN28B in governing neuroblastoma cell metabolism and suggest a potential disruption in the redox balance of LIN28B-bearing cells. This study contributes valuable insights into the molecular mechanisms underlying LIN28B-associated adverse outcomes in neuroblastoma, paving the way for targeted therapeutic interventions. The study explores how the ectopic induction of the LIN28B oncogene affects the overall gene expression pattern in the SH-SY5Y neuroblastoma tumor cell line. The Tet-on system was employed in the investigation. This study reveals that escalating LIN28B expression significantly impacts neuroblastoma cell metabolism, suggesting a disruption in redox balance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252806 | GEO | 2024/02/14

REPOSITORIES: GEO