USP7 regulates melanoma progression through PI3K/Akt/FOXO and AMPK Pathways

Background: Increasing evidence suggests that deubiquitinase USP7 participates in tumor progression by various mechanisms and serves as a potential therapeutic target. However, its functional role in melanoma remains elusive and needs to be investigated. Methods: The down-regulation of USP7 in A375 human melanoma cells was determined by high resolution liquid chromatography mass spectrometry (LC-MS/MS). The effects of USP7 expression on proliferation and apoptosis of melanoma cells were examined by western blot, Immunohistochemical and flow cytometry. Further study knock-down of USP7 in A375 cell lines, especially knockout USP7 using CRISPR-Cas9, verified USP7 regulate cell proliferation in vivo and in vitro .Western blot and qRT-PCR, Immunofluorescence were performed to investigate the mechanisms by which USP7 mediated melanoma growth through regulating the PI3K/Akt/FOXO pathways activity Results: Proteomic and western blotting analysis show that inhibition of USP7 increases expression of PRKAB1, CASP7, and PPP2R3A, attenuates expression of ATP6V0C and PEX11B. Furthermore, ATP6V0C and PEX11B are proposed to be the substrate for USP7 function. Conclusions: Our findings demonstrate that PI3K/Akt/FOXO and AMPK signaling pathways can be regulated by USP7 during melanoma progression and provide USP7 as an attractive anticancer target for melanoma.