Overcoming BET-inhibitor JQ1 resistance in aggressive non-small cell lung cancer by inducing ferroptosis via inhibition of the BRD2-FTH1 axis.

ABSTRACT: Recent studies emphasize the involvement of the nuclear H ferritin subunit (FTH1; also known as ferritin heavy chain) in DNA protection from oxidative damage and transcriptional regulation. Bromodomain and extra-terminal domain (BET) proteins act as epigenome readers for transcriptional regulation. Among them, the role of bromodomain-containing protein 2 (BRD2) in non-small cell lung carcinoma (NSCLC) remains unclear. Moreover, the clinical utilization of BET bromodomain inhibition is severely limited by different sensitivities among NSCLC subtypes. This study provides the first evidence of nuclear BRD2-FTH1 functional interplay. Nuclear FTH1 is associated with BRD2, not bromodomain-containing protein 4 (BRD4), in a panel of NSCLC cell lines and affects BRD2 protein stability only in more

SUBMITTER: Scicchitano S 

PROVIDER: S-EPMC12699187 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature