BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma.

ABSTRACT:

Background

Glioblastoma (GBM) displays remarkable cell state plasticity, a major contributor to therapeutic resistance and tumor progression. While epigenetic mechanisms play a central role in driving this plasticity, the key regulators remain poorly understood, and developing effective therapeutic strategies targeting them has been challenging.

Methods

We investigated the role of BRD2, a key regulator of NF-κB-mediated mesenchymal (MES) transition, using GBM patient-derived xenograft cell lines, CRISPR-mediated knock-in/knockout approaches, RNA-seq, and in vitro and in vivo modeling. BET inhibitors were employed to target MES gene expression and sensitize GBM to radiation therapy.

Results

We found that PTEN loss induces RelA chromatin localization and acetylation-med

SUBMITTER: Vadla R 

PROVIDER: S-EPMC12700489 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature