USP21 upregulation in cholangiocarcinoma promotes cell proliferation and migration in a deubiquitinase-dependent manner.

Ubiquitin-specific protease 21 (USP21) has been implicated in several types of cancer. It promotes or suppresses tumor growth in a cell-context dependent manner. Cholangiocarcinoma is a malignant tumor with a high mortality rate. However, the role of USP21 in cholangiocarcinoma remains unknown. Here, we identify that the level of USP21 is upregulated in cholangiocarcinoma using bioinformatics analysis and confirm this elevation in RBE cell lines. Cell counting and 5-ethynyl-2'-deoxyuridine incorporation assays reveal that USP21 promotes the proliferation of cholangiocarcinoma. Wound healing and transwell assays demonstrate that USP21 accelerates RBE cell migration. In addition, rescue assays reveal that reintroduction of USP21 wildtype other than the deubiquitinase-deficient C221A mutant restores USP21 depletion-induced attenuation in cell proliferation and migration, indicative of the requirement of the deubiquitinase activity. Collectively, these data indicate that USP21 is critically involved in cholangiocarcinoma tumorigenesis and may be an effective target for the treatment of cholangiocarcinoma.