HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma.

ABSTRACT: The role of HIF2α, encoded by EPAS1, in neuroblastoma remains controversial. Here, we demonstrate that induction of high levels of HIF2α in MYCN-amplified neuroblastoma cells results in a rapid and profound reduction of the oncoprotein MYCN. This is followed by an upregulation of genes characteristic of noradrenergic cells in the adrenal medulla. Additionally, upon induction of HIF2α, the proliferation rate drops substantially, and cells develop elongated neurite-like protrusions, indicative of differentiation. In vivo HIF2α induction in established xenografts significantly attenuates tumor growth. Notably, analysis of sequenced neuroblastoma patient samples, revealed a negative correlation between EPAS1 and MYCN expression and a strong positive correlation between

SUBMITTER: Yuan J 

PROVIDER: S-EPMC12582314 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature