The Role And Mechanism Of UBE2C In The Initiation And Development Of Liver Cancer

Background:Liver cancer is one of the most common malignant tumors worldwide.Liver cancer has an insidious onset,high degree of malignancy,strong tumor heterogeneity,difficulty in early detection,and great difficulty in late treatment,and surgery is still the main way to treat liver cancer.The rate of early diagnosis and early treatment of liver cancer patients in China is low,and the existing early screening methods are very limited,so it is great significance for the early diagnosis and treatment of liver cancer to in-depth study of key molecules and their regulatory mechanisms in the process of liver cancer occurrence and development.We found that the ubiquitin-binding enzyme UBE2 C is highly expressed in a variety of cancers through bioinformatics analysis,and literature research has observed that UBE2 C plays an important role in cell division-related factors and cyclin ubiquitination modification,but its relationship with liver cancer and related mechanisms are still unclear.Objective:To study the role,molecular mechanism and clinical significance of UBE2 C in the occurrence and development of liver cancer.Methods:Linked Omics,Oncomine,TCGA,Bioportal and other databases were used to analyze the expression characteristics of UBE2 C in liver cancer.The results of bioinformatics analysis were verified by Western Blotting and immunohistochemical analysis of liver cancer tissue samples.The lentiviral expression vectors sh UBE2 C and SMMC7721,HEPG2 hepatoma cell lines were used to construct UBE2 C silent cell lines.The relationship between UBE2 C and cell proliferation and migration and possible mechanisms of action were explored through in vitro and in vivo experiments.The R software package was used to perform differential analysis of UBE2 C co-expression genes and construct risk models and nomograms,and evaluate patient prognosis.Results:Through the analysis of multiple databases,it was found that the m RNA level of UBE2 C in liver cancer tissues was significantly upregulated.Western Blotting analysis of 55 paired clinical liver cancer tissue samples verified that the protein expression level of UBE2 C in liver cancer tissues was significantly higher than that of adjacent tissues,and immunohistochemical analysis of The Human Protein Atlas database also showed similar results.In addition,the survival analysis of Kaplan-Meier plotter and TCGA database showed that the overall survival and recurrence-free survival of patients with high expression of UBE2 C were shortened,and the ROC curve analysis in the four databases of TCGA,GSE36376,GSE10143 and GSE25097 showed that the differential diagnosis ability of UBE2 C for liver cancer was significantly better than that of the commonly used biomarker alpha-fetoprotein(AFP).UBE2 C silent cell lines were constructed using sh UBE2 C and hepatoma cell lines SMMC7721 and HEPG2.In vitro cell function experiments,mouse lung metastasis experiments and mouse tumor-bearing experiments showed that silencing UBE2 C could significantly inhibit the proliferation,migration and invasion ability of corresponding hepatoma cells.Flow cytometry detected cell cycle and apoptosis,and found that after silencing UBE2 C,the corresponding hepatoma cells developed G0/G1 phase arrest and increased apoptosis rate.GSEA pathway enrichment analysis and further in vitro experimental verification analysis showed that UBE2 C mainly regulated the activity of E2 F targets pathway by affecting the expression of CDCA8 and SPC25,which in turn affected the prognosis of patients with liver cancer.In addition,through the analysis of UBE2 C differential co-expression genes and subsequent univariate Cox analysis,Lasso regression analysis,multivariate Cox regression analysis,three genes(HMMR,UCK2,G6PD)related to the prognosis of liver cancer were finally screened and a prognostic risk model was constructed.We found that as the risk score increased,so did the risk of prognosis and survival,The prediction results of the risk model were evaluated by testing the cohort,training cohort and whole cohort,and the ROC curve showed that the prediction performance of the risk model was better.Combining pathological parameters and risk scores,we successfully build a nomogram model that can be quantitatively analyzed.Finally,we observed that the risk score of patients had a significant effect on the invasion of immune cells in the tumor microenvironment and the sensitivity of commonly used chemotherapy drugs in the clinic.Conclusion:UBE2C is an important functional gene affecting the development and prognosis of liver cancer,and the analysis of UBE2 C expression has certain guiding significance for the early diagnosis of liver cancer.UBE2 C regulates the activity of the E2 F targets pathway by affecting the expression of CDCA8 and SPC25,thereby affecting the progression of liver cancer and the prognosis of patients.