Article ABHD12 contributes to tumorigenesis and sorafenib resistance by preventing ferroptosis in hepatocellular carcinoma

Sorafenib induces ferroptosis, making it a useful treatment against advanced liver hepatocellular carcinoma (LIHC). However, sorafenib resistance is extremely common among LIHC patients. Here, we used a comprehensive approach to investigate the effects of ABHD12, which regulates tumorigenesis and sorafenib resistance in LIHC. We validated ABHD12 expression was upregulated in LIHC tissue, which correlated with worse overall survival and related to tumor size or stage. ABHD12 facilitated a pro-tumorigenic phenotype involving increased cell proliferation, migration, and clonogenicity as well as sorafenib resistance. Knockout of ABHD12 sensitized liver cancer cells to sorafenib-induced ferroptosis. Co-delivery of sorafenib and ABHD12 inhibitor into a nude mouse model enhanced therapeutic efficacy for LIHC. Our study demonstrates that ABHD12 contributes to tumor growth and sorafenib resistance in liver cancer, which indicate the promising potential of ABHD12 in diagnosis and prognosis as well as highlight the potential therapeutic applications for co-delivery of sorafenib and ABHD12 inhibitor.

Automated summary

The study found that ABHD12 is not only associated with the occurrence and development of liver hepatocellular carcinoma, but also with the resistance to Sorafenib. Knocking out ABHD12 can make liver cancer cells more sensitive to sorafenib-induced ferroptosis. The results of the study suggest that ABHD12 may be a potential target for the diagnosis, prognosis, and treatment of liver cancer.