The purposes of this study were therefore to determine the clinical significance of USP22 expression in iCCA, to evaluate the role of USP22 in controlling tumour growth in vitro and in vivo, and to study the underlying molecular mechanisms by which USP22 operates linking SIRT1 for the epigenetic deubiquitination and deacetylation to CCA progression. Here, SIRT1 is linked to cholangiocarcinoma.