EZH2, a
histone methylase, plays a critical role in the
tumor progression via regulation of progenitor genes. However, the detailed molecular mechanism of EZH2 in
cancer malignant progression remains unknown. Therefore, we aimed to investigate how EZH2 is regulated in human
cancer. We used numerous approaches, including Co-immunoprecipitation (Co-IP), Transfection, RT-PCR, Western blotting, Transwell assays, and animal studies, to determine the deubiquitination mechanism of EZH2 in
cancer cells. We demonstrated that USP7 regulated EZH2 in human
cancer cells and in vivo in mouse models. Overexpression of USP7 promoted the expression of EZH2
protein, but overexpression of a USP7 mutant did not change the EZH2 level. Consistently, knockdown of USP7 resulted in a striking decrease in EZH2
protein levels in human
cancer cells. Functionally, USP7 overexpression promoted cell growth and invasion via deubiquitination of EZH2. Consistently, downregulation of USP7 inhibited cell migration and invasion in
cancer. More importantly, knockdown of USP7 inhibited
tumor growth, while USP7 overexpression exhibited opposed effect in mice. Our results indicate that USP7 regulates EZH2 via its deubiquitination and stabilization. The USP7/EZH2 axis could present a new promising therapeutic target for
cancer patients.