METTL3/MYCN cooperation drives neural crest differentiation and provides therapeutic vulnerability in neuroblastoma.

ABSTRACT: Neuroblastoma (NB) is the most common extracranial childhood cancer, caused by the improper differentiation of developing trunk neural crest cells (tNCC) in the sympathetic nervous system. The N⁶-methyladenosine (m⁶A) epitranscriptomic modification controls post-transcriptional gene expression but the mechanism by which the m⁶A methyltransferase complex METTL3/METTL14/WTAP is recruited to specific loci remains to be fully characterized. We explored whether the m⁶A epitranscriptome could fine-tune gene regulation in migrating/differentiating tNCC. We demonstrate that the m⁶A modification regulates the expression of HOX genes in tNCC, thereby contributing to their timely differentiation into sympathetic neurons. Furthermore, we show that

SUBMITTER: Thombare K 

PROVIDER: S-EPMC11649786 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature