Neddylation inhibition induces DNA double-strand breaks, hampering tumor growth in vivo, and promotes radiosensitivity in PAX3-FOXO1 rhabdomyosarcoma.

ABSTRACT: Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma with myogenic features affecting children and adolescents. The high-risk fusion-positive RMS subtype (FP-RMS), driven by the oncogenic chimeric transcription factor PAX3-FOXO1, shows 5-year overall survival not exceeding 30%. Here, we examine the impact of neddylation inhibition, a post-translational modification in which the NEDD8 peptide is conjugated to proteins, on the tumorigenic properties of FP-RMS. Here, we report that the NAE1 and UBA3 genes encoding the two subunits of the NEDD8-activating enzyme (NAE) heterodimer are upregulated in FP-RMS patients compared to healthy skeletal muscle tissues and highly expressed in RMS among several tumor types. Furthermore, DepMap analyses showed that FP-RMS cell lines are among the mos

SUBMITTER: Aiello FA 

PROVIDER: S-EPMC12583468 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature