Pharmacological Inhibition of USP7 Supresses Growth and Metastasis of Melanoma Cells in Vitro and in Vivo

Abstract

Background: Melanoma is a highly aggressive type of skin cancer. Due to the development of diverse resistance mechanisms and severe adverse side effects, significantly limits the efficiency of current therapeutic approaches. Identification of the new therapeutic targets involved in the pathogenesis will benefit to develop novel therapeutic strategies. The deubiquitinase USP7(ubiquitin-specific protease-7) is deregulated in serval cancer types, as a potential target for cancer treatment, but its role in melanoma is still unclear. Here, we investigated the role of USP7 and its inhibitor P22077 in melanoma treatment.Methods: To explore the role of USP7 and the anti-tuomr effect of P22077 in melanma progression and metastasis, a series of cell biological, molecular and biochemical approaches were used for in vitro and in vivo investigations.These methods included RT-qPCR, Western blot assay, cell transfection, CCK8 assay, flow cytometry, scratch test, Transwell assay, mouse xenograft,TUNEL staining.Results:The USP7 inhibitor P22077 suppressed the growth of melanoma in vitro and in vivo. additionally, P22077 induction of cell cycle arrest and apoptosis via ROS(reactive oxygen species) accumulation-induced DNA damage. Furthermore, inhibition of USP7 also prevented migration and invasion of melanoma cells in vitro and in vivo by decrease the Wnt/β-catenin signal pathway. Conclusion: Our data indicated that USP7 acts as an oncogene involved in melanoma cell proliferation and metastasis and may provide a novel therapeutic target for melanoma treatment.