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) 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 tNCCs. We demonstrate that the m6A modification regulates the expression of HOX genes in tNCCs, thereby contributing to their timely differentiation into sympathetic neurons. Furthermore, we show that posterior HOX genes are m6A-modified in MYCN-amplified neuroblastoma w

SUBMITTER: Ketan Thombare 

PROVIDER: S-SCDT-10_1038-S44318-024-00299-8 | biostudies-other |

REPOSITORIES: biostudies-other