USP18 directly regulates Snail1 protein through ubiquitination pathway in colorectal cancer

Abstract

Abstract Background Colorectal cancer (CRC) is one of the most common digestive malignant tumors in the world. Ubiquitin-specific peptidase 18 (USP18) plays a regulatory role in tumorigenesis, and abnormal expression of Snail1 is also believed to be related to tumorigenesis. However, whether USP18 could affect colorectal cancer through Snail1 remains unclear. This study was designed to investigate the role of USP18 in colorectal cancer. Methods USP18 protein and mRNA abundance in clinical tissues and five cell lines were analyzed with quantitative real-time PCR (qRT-PCR) and western blot. USP18 overexpression-treated DLD1 cells and USP18 knockdown-treated SW480 cells were used to study cell proliferation, migration, invasion, and the expression of epithelial-mesenchymal transformation (EMT) biomarkers. Moreover, ubiquitination-related Snail1 degradation was detected with qRT-PCR and western blot. The relationships between USP18 and Snail1 were investigated with western blot, co-immunoprecipitation, migration, and invasion. Results USP18 was highly expressed in colorectal cancer tissues. Overexpression of USP18 could promote proliferation, colony formation, migration, and invasion of colorectal cancer cells. Overexpression of USP18 effectively promoted cell survival after treatment with three different chemotherapy drugs. Moreover, USP18 could regulate Snail1 degradation through ubiquitination pathway. Furthermore, we demonstrated that Snail1 could effectively reverse the influence of USP18 on cell proliferation, migration, invasion, and EMT of CRC cells. Conclusion USP18 could promote the proliferation, migration, and invasion of colorectal cancer by deubiquitinating and stabilizing the Snail1 protein in colorectal cancer.

Keywords

• Colorectal cancer
• EMT
• Snail1
• USP18
• qRT-PCR