Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma.

ABSTRACT:

Background

Altered branched-chain amino acid (BCAA) metabolism modulates epigenetic modification, such as H3K27ac in cancer, thus providing a link between metabolic reprogramming and epigenetic change, which are prominent hallmarks of glioblastoma multiforme (GBM). Here, we identified mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), an enzyme involved in leucine degradation, promoting GBM progression and glioma stem cell (GSC) maintenance.

Methods

In silico analysis was performed to identify specific molecules involved in multiple processes. Glioblastoma multiforme cells were infected with knockdown/overexpression lentiviral constructs of HMGCL to assess malignant performance in vitro and in an orthotopic xenograft model. RNA sequencing was used to identify

SUBMITTER: Sun Y 

PROVIDER: S-EPMC10995515 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature