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The Expression Of OIP5 Gene And Its Relationship With Arsenic Trioxide In Renal Cell Carcinoma

Posted on:2015-01-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:M C GongFull Text:PDF
GTID:1314330533451368Subject:Surgery
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Objective:Opa interacting protein 5(OIP5),overexpressed in some types of human cancers,has been reported to be associated with the carcinogenesis of human cancer.However,the biological function and clinical significance of OIP5 in human Clear cell renal cell carcinoma(CCRCC)remains unknown.Therefore,this study aimed to investigate the expression and function of OIP5 in renal cell carcinoma tissue and renal cell carcinoma cell lines,as well as study the role of OIP5 specific siRNA in combination with arsenic trioxide in cell apoptosis.In order to find a biomarker for renal cell carcinoma and provide a theoretical basis for gene therapy of renal cell carcinoma.Methods: We used RT-PCR to detect the OIP5 expression in renal cell carcinoma tissues and adjacent normal tissues.In 103 cases of paraffin-embedded renal cell carcinoma tissues,we applied immunohistochemical methods to detect the expression of OIP5,and analyze the relationship between the clinical and pathological features with OIP5.In addition,we silenced OIP5 in renal carcinoma cell lines and then detected the cell proliferation activity by CCK8 and clonogenic assay.Finally,we examined the cell proliferation activity used CCK8 after treated with the OIP5 specific siRNA combined with arsenic trioxide.Results: In the present study,we found the expression of OIP5 was markedly upregulated in surgical CCRCC specimens and CCRCC cell lines.Immunohistochemical analysis revealed that paraffin-embedded archival CCRCC specimens exhibited higher levels of OIP5 expression than normal renal tissues.Further statistical analysis suggested the upregulation of OIP5 was positively correlated with the Fuhrman grade(P=0.02),T classification(P=0.015),Nclassification(P=0.018)and clinical stage(P=0.035).Also,patients with high OIP5 expression dramatically exhibited shorter survival time(P=0.001).In addition,the OIP5 expression was an independent prognostic marker of overall survival of CCRCC patients in a multivariate analysis(P=0.008).Experimentally,we demonstrated that silencing OIP5 in CCRCC cell lines by specific siRNA clearly inhibited cell growth.Moreover,silencing OIP5 by specific siRNA combined with arsenic trioxide can inhibit cell proliferation and induce apoptosis more strongly.Conclusions: Our study is the first one showed that OIP5 was highly expressed in renal cell carcinoma tissues and cell lines.Silencing OIP5 effectively inhibited the proliferation of renal cell carcinoma cells.In addition,our research showed that OIP5 is both a clinical progression of renal cell carcinoma,but also a prognostic biomarker of overall survival in patients with renal cell carcinoma.Silencing OIP5 combined with arsenic trioxide can inhibit cell proliferation more effectively.
Keywords/Search Tags:OIP5, clear cell renal cell carcinoma, siRNA, arsenic trioxide
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