Expression And Mechanism Of UBE2Z In Hepatocellular Carcinoma

Background and objective:Hepatocellular carcinoma is the most frequent malignant tumors around the world.The incidence and mortality of HCC in China are very high,which have severely threatened human health.Most patients with HCC fail to grasp at the chance of receiving radical treatment owing to their disease usually being advanced or metastatic at the time of diagnosis.Early detection,diagnosis and treatment are important to improve the prognosis of patients with liver cancer.Mounting studies suggest that most enzymes involved in ubiquitination are critically involved in tumorigenesis.Ubiquitin conjugating enzyme E2Z(UBE2Z),also known as USE1,is a member of the E2 enzymes.However,compared with others E2 enzymes,there is little or no report about the roles of UBE2 Z in cancer.In this work,we aim to investigate the expression level of UBE2 Z in liver cancer and analyze the correlation between the expression level of UBE2 Z and the prognosis of HCC patients,to examine the proliferation,migration and invasion of HCC in vitro after UBE2 Z knockdown and explore the possible mechanisms.Methods:1.The microarray data was obtained from TCGA database and Ocomine database.The UBE2 Z expression in the tumor tissues and the adjacent non-tumoral tissues was illustrated by scatterplot.Kaplan-Meier analysis of the correlation between UBE2 Z expression level and overall survival or Disease-free survival in the TCGA cohort.2.The copy number alteration of UBE2 Z and its DNA methylation data in HCC were extracted from UCSC Xena Browser.The heatmaps were utilized to show the relationships between UBE2 Z expression and its CNAs and its DNA methylation in patients with HCC.3.The UBE2 Z protein expression in the tumor tissues and the adjacent non-tumoral tissues in 60 cases of HCC patients were detected by Immunohistochemistry staining.And its expression in liver cancer cells were detected by Western-Blot.4.The role of UBE2 Z in the migration,and invasion capabilities of HCC cells evaluated by using cell counting kit-8(CCK8),wound healing assay and transwell assay.Results:1.UBE2 Z was upregulated in HCC,and was closely related to the prognosis,and it can be used as an independent prognostic risk factor of HCC.2.UBE2 Z expression was linked to its DNA amplification and was modulated in part by its DNA methylation.3.Knockdown of UBE2 Z reduced proliferation,migration and invasion of HCC cells.4.UBE2 Z might promote HCC progression by targeting ERK and stat3 signaling pathway.