USP43 directly regulates ZEB1 protein, mediating proliferation and metastasis of colorectal cancer

Colorectal cancer is one of the most common malignant tumors of the digestive tract. In this study, we had examined the biological role of USP43 in colorectal cancer. USP43 protein and mRNA abundance in clinical tissues and five cell lines were analyzed with quantitative real-time PCR test (qRT-PCR) and western blot. USP43 overexpression treated DLD1 cells and USP43 knockdown treated SW480 cells were used to study cell proliferation, migration, colony formation, invasion, and the expression of epithelial-mesenchymal transformation (EMT) biomarkers. Moreover, ubiquitination related ZEB1 degradation was studied with qRT-PCR and western blot. The relationships between USP43 and ZEB1 were investigated with western blot, co-immunoprecipitation, migration, and invasion. USP43 was highly expressed in colorectal cancer tissues. USP43 overexpression and knockdown treatments could affect cell proliferation, colony formation, migration, invasion, and the expression of EMT associated biomarkers. Moreover, USP43 can regulate ZEB1 degradation through ubiquitination pathway. USP43 could promote the proliferation, migration, and invasion of colorectal cancer. Meanwhile, USP43 can deubiquitinate and stabilize the ZEB1 protein, which plays an important role in the function of colorectal cancer.