GINS4 suppresses ferroptosis by antagonizing p53 acetylation with Snail

Abstract

Ferroptosis is an iron-dependent oxidative, nonapoptotic form of regulated cell death caused by the destruction of redox homeostasis. Recent studies have uncovered complex cellular networks that regulate ferroptosis. GINS4 is a promoter of eukaryotic G 1 /S - cell cycle as a regulator of initiation and elongation of DNA replication, but little is known about its impact on ferroptosis. Here, we found that GINS4 was involved in the regulation of ferroptosis in lung adenocarcinoma (LUAD). CRISPR/Cas9-mediated GINS4 KO facilitated ferroptosis. Interestingly, depletion of GINS4 could effectively induce G1, G 1 /S, S, and G 2 /M cells to ferroptosis, especially for G2/M cells. Mechanistically, GINS4 suppressed p53 stability through activating Snail that antagonized the acetylation of p53, and p53 lysine residue 351 (K351 for human p53) was the key site for GINS4-suppressed p53-mediated ferroptosis. Together, our data demonstrate that GINS4 is a potential oncogene in LUAD that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD.

Identification and validation of ferroptosis related genes in prostate cancer cells under erastin exposure

“…Our findings indicated that erastin remarkably reduced the proliferative activity of PCa cells. In addition, Fe 2+ is one of the essential factors of DNA replication, which is vital for cell survivability [38][39][40]. Consequently, we believed that erastin primarily transforms PCa cell proliferation by altering DNA replication.…”