USP22 is an enzyme involved in histone modification, primarily by removing the monoubiquitin group from lysine 120 of H2B (H2Bub1).28,29 Increased USP22 has been correlated with worse outcomes in several cancers, such as pancreatic cancer,30 lung adenocarcinoma,31 and OC.19 Knockdown of USP22 in OC cells inhibits cell proliferation in vitro and tumor growth in vivo, indicating that USP22 is a potential therapeutic target for treating OC.19 Consistently, in this study, depletion of USP22 repressed cell proliferation, migration, invasion, and EMT in OC. This evidence concerns the gene H2BC21 and familial pancreatic carcinoma.