USP1 regulates esophageal cancer progression through CDC25A deubiquitination to regulate CDK1 expression

Cell division cycle 25 A (CDC25A) is a key regulatory molecule of the cell cycle. However, the expression of CDC25A and its importance in esophageal cancer remain unclear. In this study, we found that CDC25A was highly expressed in esophageal cancer tissues utilizing the Cancer Genome Atlas (TCGA) database, Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). By detecting cell proliferation, migration, invasion and apoptosis, it was observed that knockdown of CDC25A inhibited cell proliferation, migration and invasion and promoted apoptosis. By screening for deubiquitinating enzymes, ubiquitin-specific peptidase 1 (USP1) was identified as a deubiquitinating enzyme that bound to, deubiquitinated and stabilized the CDC25A protein. We also showed that CDC25A targeted cyclin-dependent kinase 1 (CDK1) to promote cell proliferation. Furthermore, USP1 knockdown suppressed xenografted tumor growth in nude mice, whereas overexpression of CDK1 promoted tumor growth. In conclusion, our findings suggest that the USP1/CDC25A/CDK1 axis influences esophageal carcinogenesis and progression.

The online version contains supplementary material available at 10.1007/s13205-025-04663-1.