Inhibition of microglial EZH2 leads to anti-tumoral effects in pediatric diffuse midline gliomas.

ABSTRACT:

Background

Diffuse intrinsic pontine gliomas (DIPG), within diffuse midline gliomas are aggressive pediatric brain tumors characterized by histone H3-K27M mutation. Small-molecule inhibitors for the EZH2-H3K27 histone methyltransferase have shown promise in preclinical animal models of DIPG, despite having little effect on DIPG cells in vitro. Therefore, we hypothesized that the effect of EZH2 inhibition could be mediated through targeting of this histone modifying enzyme in tumor-associated microglia.

Methods

Primary DIPG tissues, and cocultures between microglia and patient-derived DIPG or -pediatric high-grade glioma (pHGG) cell lines, were used to establish the H3-K27M status of each cell type. Antisense RNA strategies were used to target EZH2 gene expressi

SUBMITTER: Keane L 

PROVIDER: S-EPMC8409254 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature