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The Low Expression And Mechanism Of MicroRNA-184in Human Renal Cell Carcinoma

Posted on:2014-02-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y C LuoFull Text:PDF
GTID:1264330401955251Subject:Surgery
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Renal cell carcinoma(RCC) original from renal tubule epidermis, it is one of the most common malignant tumor in adult urinary system. The mechanism of RCC was not clarified enough yet. An important feature of RCC is not sensitive to traditional radioactive and drug treatment, this feature restrict the treatment of RCC. In transferred RCC, the five year survival rate is less than10%, and the two year survival rate is less than20%. Research the mechanism of RCC, searching an effective signal gene for diagnosis and target treatment is significative.MicroRNAs are a class of18~26nt small non-coding single strand RNA molecules, which negatively regulate the expression of a variety of genes at post-transcriptional levelby binding to complementary sites on target mRNA. Mutation, deletion or high expression of microRNA was found to correlate with various human cancers. MicroRNAs involved in tumor cell proliferation, differentiation and apoptosis processes as function as oncogenes or tumor supressors. It is predictable that microRNA might be applied in the diagnosis and treatment of malignant tumors.MicroRNA-184was found suppressed in neuroblastoma, and when enhancing the expression of microRNA-184, neuroblastoma cell proliferation can be suppressed. In RCC, Leng et al found that microRNA-184was suppressed similarly, indicating that microRNA-184might be a suppressor of RCC, but no forward research about it was done. Our task goal is explore the effect of microRNA-184in RCC and its mechanism. Part Ⅰ The expression and significance of microRNA-184and AKT2in RCCPurposes1explore the expression of microRNA-184in RCC.2explore the expression of AKT2in RCC.Methods1The expression of microRNA-184in baldder cancer and matched tumor-adjacent urothelium were examined using realtime-PCR.2The expression of AKT1,AKT2in baldder cancer and matched tumor-adjacent urothelium were examined using realtime-PCR.3Using18.0SPSS software package to statistically analyze the relationship between the expression of microRNA-184and AKT2.Results1The expression of microRNA-184in RCC was lower than tumor adjacent urothelium.2The expression of AKT2in RCC was higher than tumor adjacent urothelium.3the expression level of microRNA-184in RCC was related to AKT2expression level.Conclusion1MicroRNA-184was suppressed in RCC.2AKT2expression was increased in RCC PartⅡ The effection of microRNA-184to AKT2expression in RCCPurposes1Explore the effection of enhancing the microRNA-184to the expression of AKT2in RCC.2Analyze the molecular mechanism of the role of microRNA-184in RCC.Methods1Retroviral production and infection were performed to establish stable up-regulation microRNA-184RCC cell line.2Examing the expression of AKT1, AKT2, p-AKT1, p-AKT2and PI3K in up-regulation microRNA-184RCC cell line. Analyzing the effection of microRNA-184to AKT2in RCC.Results1up-regulating the expression of microRNA-184can suppress the expression of AKT2in RCC.2up-regulating the expression of microRNA-184can suppress the activation of AKT2in RCC.Conclusion1microRNA-184can suppress the expression and activation of AKT2.2microRNA-184can regulate the occurrence and progress of RCC by suppressing the PI3K/AKT molecular signal access. PartⅢ The effection of microRNA-184to the biological behavior of RCC cellPurposes1Explore the effection of microRNA-184to the proliferation of RCC cells.2Explore the effection of microRNA-184to the migration and invasion of RCC cells.Methods1Examing the apoptosis of RCC cell after up-regulate microRNA-184by flow cytometry experiment.2Using MTT method to exam the proliferation after up-regulate microRNA-184.3Using Transwell method to exam the ability of migration and invasion of RCC cell after up-regulate microRNA-184.Results1Flow cytometry experiment show that up-regulating microRNA-184resulted an significant increase in apoptosis of RCC cells.2MTT show that the proliferation of RCC cells was suppressed after up-regulate microRNA-184.3After up-regulate microRNA-184, the migration and invasion of RCC cells descended significantly.Conclusion1up-regulating the expression of microRNA-184can suppress the proliferation of RCC cells.2up-regulating the expression of microRNA-184can enhance the apoptosis of RCC cells.3up-regulating the expression of microRNA-184can suppress the migration and invasion of RCC cells.
Keywords/Search Tags:microRNA-184, renal cell cancer, target treat, AKT2
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