MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells.

ABSTRACT: The MYCN gene has a critical role in determining the clinical behavior of neuroblastoma. Although it is known that genomic amplification occurs in high-risk subsets, it remains unclear how MYCN expression is regulated in the pathogenesis of neuroblastomas. Here, we report that MYCN expression was regulated by the oncoprotein MDM2 at the post-transcriptional level and was associated with neuroblastoma cell growth. Increasing MDM2 by ectopic overexpression in the cytoplasm enhanced both mRNA and protein expression of MYCN. Mechanistic studies found that the C-terminal RING domain of the MDM2 protein bound to the MYCN mRNA's AREs within the 3'UTR and increased MYCN 3'UTR-mediated mRNA stability and translation. Conversely, MDM2 silencing by specific siRNA rendered the MYCN mRNA unstable and r

SUBMITTER: Gu L 

PROVIDER: S-EPMC3213308 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature