ZDHHC12 (Zinc Finger DHHC-Type Palmitoyltransferase 12)

ZDHHC12 knockdown restores PARP1 trapping and resensitizes resistant cells and xenografts to Niraparib. These findings establish ZDHHC12-mediated PARP1 palmitoylation as a targetable vulnerability to overcome PARPi resistance.

A prognostic model based on palmitoylation-related genes offers a valuable tool for survival prediction and the development of personalized treatment strategies in LUAD. ZDHHC5, a key gene related to palmitoylation, demonstrates potential as both a therapeutic target and a prognostic marker for LUAD and other cancers.

This study reveals that ZDHHC12 is a critical mediator of PA-induced HCC progression and that targeting HDAC8 can suppress this process. These findings offer a potential therapeutic strategy for HCC patients with high dietary intake of SFAs, particularly PA.

Markedly, ZDHHC12 inhibition significantly augmented the anti-tumor activity of cisplatin in an ovarian cancer xenograft tumor model, as well as in an ascites-derived organoid line of platinum-resistant ovarian cancer. Our data suggest the potential of ZDHHC12 as a promising target to improve the outcome of HGSOCs in response to platinum-based chemotherapy.

These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism.

Our results suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH-HCC. Obese NASH-HCC may be driven by hypomethylation of Wnt signaling pathway-related genes, while progression of lean NASH-HCC may be driven by other signaling pathways, including lipid metabolism.