Lysine demethylase 5D promotes CHEK1 inhibitor sensitivity through p38-mediated cyclooxygenase-2 expression in castration-resistant prostate cancer cells.

ABSTRACT: CHEK1 (CHK1) is a key regulator of the G2/M checkpoint and DNA damage response. Although CHK1 inhibitors (CHK1is) show promise in multiple clinical trials, their further advancement is hampered by the lack of reliable predictive biomarkers. Our previous study demonstrated a nearly 20-fold difference in the sensitivity to a clinical-stage CHK1i SRA737 in prostate cancer (PC) cells. Through bioinformatics analysis, an epigenetic regulator, lysine demethylase 5D (KDM5D), was identified as a potential mediator of differential responses to SRA737. Gain- or loss-of-function studies were performed to investigate how altered KDM5D expression affects CHK1i sensitivity and the underlying mechanisms. Our data demonstrated that higher KDM5D expressions correlated with greater sensitivity to CHK1is in

SUBMITTER: Zheng W 

PROVIDER: S-EPMC12799561 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature