Bromodomain-containing protein 4 (BRD4) as an epigenetic regulator of fatty acid metabolism genes and ferroptosis.

ABSTRACT: Reprogramming lipid metabolism is considered a fundamental step in tumourigenesis that influences ferroptosis. However, molecular mechanisms between lipid metabolism and ferroptosis remain largely unknown. Results from the drug screening of 464 inhibitors (for 164 targets) applied to ferroptosis cells indicated that 4 inhibitors targeted bromodomain-containing protein 4 (BRD4) significantly inhibiting erastin-induced ferroptosis. Functional studies proved that the loss of BRD4 weakened oxidative catabolism in mitochondria, protecting cells from the excessive accumulation of lipid peroxides. Mechanism research revealed that the transcriptional levels of fatty acid metabolism-related genes (HADH, ACSL1 and ACAA2) participating in the β-oxidation of fatty acids (FAO) and polyunsaturated fatty

SUBMITTER: Yang M 

PROVIDER: S-EPMC9617950 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature