Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and the tumor suppressor p53 has a crucial role in CRC progression. Ubiquitin-specific protease 36 (USP36), a member of the deubiquitinating enzyme family, contributes to tumor development in various cancers. However, the mechanisms through which USP36 influences the p53 signaling pathway in CRC are not fully understood. In this study, we observed that USP36 expression was elevated in CRC tissues and correlated with worse clinical outcomes. Functionally, high USP36 enhanced CRC cell growth, migration, and invasion in both in vitro and in vivo models. Mechanistically, USP36 interacted with RBM28 and stabilized it via deubiquitination at the K162 residue. In turn, increased RBM28 inhibited p53 transcriptional activity, suppressing the p53 signaling pathway. Collectively, our results reveal a previously unrecognized USP36/RBM28/p53 axis that promotes CRC progression and may represent a potential therapeutic target.
