Ubiquitin-specific proteases as key regulators in the malignant progression and therapy resistance of colorectal cancer: current insights and future perspectives

As a member of the DUBs (deubiquitinating enzymes) family, USPs (ubiquitin-specific peptidases) play a crucial regulatory role in the occurrence and progression of various malignancies. This review summarizes the current research on USPs in colorectal cancer, with a focus on the involvement of different USPs as either oncogenes or tumor suppressor genes in regulating the malignant progression of colorectal cancer. We discuss in detail the regulatory role of USPs in the process of drug resistance in tumors, the signaling pathways regulated by USPs, the correlation between different USP expression levels and early diagnosis and prognostic evaluation, as well as the latest research developments in USP inhibitors. Mechanistically, USPs regulate key proteins in several signaling pathways, including Wnt, P53, and PI3K/Akt/mTOR, highlighting their significant role in the malignant progression of colorectal cancer. Finally, we further discuss the functional and mechanistic differences among various USPs, the challenges faced in developing USP inhibitors, and prospects for future research directions.