Deubiquitinating Enzyme USP7 Regulates The Progression Of Hepatocellular Carcinoma By Stabilizing Aurora B

Objectives:Although the importance of deubiquitinating enzyme 7(USP7)in cancer development is well established,its role and potential mechanisms in hepatocellular carcinoma(HCC)remain largely unknown.Aurora B also plays an important role in HCC progression,yet the regulatory mechanisms controlling its protein stability in HCC are unknown.In this study,we used the Ubi Brower website to predict the deubiquitinating enzyme USP7 upstream of Aurora B.We then investigated the molecular mechanism of deubiquitinating enzyme regulation of Aurora B protein stability and its biological function in tumor development.Methods: 1.Immunoprecipitation was used to detect whether USP7 interacts with Aurora B.2.Real-time fluorescence quantitative PCR was used to detect the effect of USP7 on the m RNA expression level of Aurora B.3.The effect of USP7 and Aurora B on the proliferation and migration of hepatocellular carcinoma was examined using CCK-8,transwell and scratch assays.5.The effect of USP7 and Aurora B inhibitors on the treatment of subcutaneous tumours in nude mice was examined.6.Immunohistochemical assays were used to examine the correlation between USP7 and Aurora B expression in clinical tissue samples of HCC and their relationship with patient survival.Results: 1.Immunoprecipitation assays determined the interaction between USP7 and Aurora B.2.Ubiquitination-related assays confirmed that USP7 deubiquitinates Aurora B and is dependent on its deubiquitinating enzyme activity.3.It was demonstrated that USP7 promotes cell proliferation and migration and that knockdown of Aurora B counteracts this pro-proliferation and migration phenomenon.4.Immunohistochemistry showed that both USP7 and Aurora B were highly expressed in hepatocellular carcinoma tissues compared to normal liver tissues,and that USP7 and Aurora B expression were positively correlated,and that high expression of USP7 and Aurora B was associated with poor prognosis in HCC patients.It was found that high expression of USP7 and Aurora B was associated with poor prognosis in HCC patients and could be used as an independent predictor.Conclusions: USP7 interacts with Aurora B and ubiquitinates Aurora B by relying on its deubiquitinating enzyme activity.USP7 also promotes cell proliferation and migration by regulating Aurora B protein stability.These findings reveal a role for the USP7-Aurora B axis in driving hepatocellular carcinoma,which may be further developed into a new therapeutic strategy for hepatocellular carcinoma.