Oncometabolite D-2HG drives tumor metastasis and protumoral macrophage polarization by targeting FTO/m⁶A/ANGPTL4/integrin axis in triple-negative breast cancer.

ABSTRACT:

Background

D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported the diverse effects of D-2HG in pathophysiological processes, yet its role in breast cancer remains largely unexplored.

Methods

We applied an advanced biosensor approach to detect the D-2HG levels in breast cancer samples. We then investigated the biological functions of D-2HG through multiple in vitro and in vivo assays. A joint MeRIP-seq and RNA-seq strategy was used to identify the target genes regulated by D-2HG-mediated N6-methyladenosine (m⁶A) modification. RNA pull-down assays were further applied to identify the reader that could specifically recognize the m⁶A modification on angiopoietin like 4 (ANGPTL4) mRNA and

SUBMITTER: Zhang S 

PROVIDER: S-EPMC11800637 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature