USP11 Facilitates Colorectal Cancer Proliferation and Metastasis by Regulating IGF2BP3 Stability.

The abnormal expression of ubiquitin-specific protease 11 (USP11) is thought to be related to tumor development and progression; however, few studies have reported the biological function and clinical importance of USP11 in colorectal cancer (CRC). Therefore, it is necessary to further explore the role of USP11 in CRC. Immunohistochemical staining was used to explore the association between prognosis and USP11 expression in CRC. Cholecystokinin octapeptide (CCK-8), colony formation, transwell, and animal assays were used to study the abilities of proliferation, migration, and invasion in CRC cells. Co-immunoprecipitation assays, Western blotting, ubiquitination assays, and rescue experiments were performed to elucidate the interaction between USP11 and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3). We verified that USP11 was overexpressed in CRC tissues and was associated with the depth of tumor invasion and metastasis. USP11 knockdown or overexpression could weaken or reinforce the abilities of proliferation, migration, and invasion in CRC cells in vivo or in vitro. IGF2BP3 was protected by USP11 from degradation via deubiquitination. The rescue experiments revealed that IGF2BP3 overexpression could effectively reverse the decrease in cell proliferation, migration, and invasion caused by USP11 knockdown. Therefore, USP11 might be involved in CRC tumorigenesis and development through a USP11-IGF2BP3 axis pathway, and USP11 overexpression might be a novel indicator for poor prognosis and a potential therapeutic target in CRC patients.