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Study Of RNF5 Promoting Proliferationinvasion And Metastasis In Hepatocellular Carcinoma

Posted on:2020-12-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:1484306554476284Subject:Surgery
Abstract/Summary:PDF Full Text Request
Part ?: High expression of RNF5 in HCC is closely related to the malignant prognosis of patientsObjective:To investigate the expression of RNF5 in hepatocellular carcinoma and its clinicopathological significance.and prognosis of patients with hepatocellular carcinoma(HCC).Methods:The m RNA(70 pairs)and protein(67 pairs)of RNF5 in cancer tissuesandparacancerous tissues weredetected by RT-PCR and immunohisto--chemistryrespectively,to analyze the correlation between the expression of RNF5 in cancer and the clinicopathological characteristics of patients and its influence on the prognosis Results:RNF5 m RNA expression levelsin cancer tissueswere significantly higher than that in adjacent tissues(p<0.001).and the expression of RNF5 protein levels in the cancer tissue were also significantly higher than that in adjacent tissues(p = 0.002),and the expression of RNF5 levels were closely related to tumor size(p = 0.030),the satellite lesions(p=0.017)and AFP(p=0.030)of in HCC patients.The higher the expression of RNF5 protein in liver cancer tissues,the worse the survival.The regression analysis of Cox risk factors showed that the higher expression of RNF5 protein was an independent risk factor for the prognosis of primary liver cancer(p=0.021).Conclusion:The abnormally high expression of RNF5 in HCC is related to the indicators of proliferation and metastasis of HCC patients,and the high expression of RNF5 will bring worse prognosis to patients.Therefore,RNF5 can be used as an important prognostic indicator of hepatocellular carcinoma and is expected to be a new target for systemic treatment of HCC.Part ?: RNF5 promotes hepatocellular carcinoma proliferation and metastasisObjective:To study the effect of RNF5 on the proliferation,invasion and metastasis of hepatocellular carcinoma cells and explore the possible mechanism.To investigate the effect of RNF5 on HBV-associated hepatitis and liver fibrosis.Methods: Hepatoma cell lines with stable overexpression and knocking down RNF5 were constructed,CCK8,clone formation,apoptosis assay and Transwell chamber assay were performed to investigate the effect of RNF5 on the proliferation,invasion and metastasis of HCC cells.The mechanism of RNF5 was studied by mass spectrometry and CO-IP.The role of RNF5 in the process of HBV-related hepatitis and liver fiber was studied through the establishment of animal models and clinical specimens.Results: Overexpression of RNF5 promoted the proliferation,invasion and metastasis of SMMC-7721 and SK cells,while knockdown of endogenous RNF5weakened the proliferation,invasion and metastasis of PLC and Huh7 cells.After infection with human HBV,RNF5 was slightly expressed in the liver tissue of tree shrews,with a positive rate of 72%.However,RNF5 was slightly expressed in liver tissues without HBV infection,with a positive rate of 28%.The difference in positive rates between the two groups was statistically significant(p<0.001).No expression of RNF5 was detected in animal models of cirrhosis induced by carbon tetrachloride and liver biopsy specimens of patients with liver fibrosis.Cell experiments showed that RNF5 may play a role in promoting cancer by stabilizing ATP1A1.Conclusion: The experiment confirmed that RNF5 can promote the proliferation and metastasis of Hepatoma cell lines,and inhibiting the expression of RNF5 can inhibit the proliferation,invasion and metastasis of HCC,so RNF5 can be a new target for the treatment of hepatocellular carcinoma.
Keywords/Search Tags:RNF5, hepatocellular carcinoma, prognosis, proliferation, metastasis
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