SUPR
The Spliceosome in Neuroblastoma
Dnr:

NAISS 2024/22-559

Type:

NAISS Small Compute

Principal Investigator:

Johan Holmberg

Affiliation:

UmeƄ universitet

Start Date:

2024-05-02

End Date:

2025-06-01

Primary Classification:

30108: Cell and Molecular Biology

Webpage:

Allocation

Abstract

Pre-mRNA splicing is essential for intron removal and to increase the repertoire of gene products. If not properly regulated, mis-splicing can generate altered, potentially oncogenic proteins. Several cancers harbor monoallelic mutations of spliceosome factors while MYC-driven breast cancer exhibits an increase in precursor mRNA synthesis resulting in an increased burden on the spliceosome and sensitivity to spliceosome inhibition. In a recent study, we could show that high expression levels of spliceosome factors are closely correlated with high-risk NB and poor clinical outcome. In addition, we were able to target the spliceosome and inhibit tumor growth in a xenograft NB model utilizing spliceosome inhibitors. We will now through ONT analyze the consequences of splicesome inhibiton on the expression of splice isoforms in neuroblastoma xenografts.