USP22 and cholangiocarcinoma: In 2021, Tian et al. first demonstrated that USP22 deubiquitinates and stabilizes SIRT1, thereby activating the Akt/ERK pathway, inducing the epithelial-to-mesenchymal transition (EMT), suppressing apoptosis, and markedly promoting proliferation, invasion, and metastasis of CCA cells [55].