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Molecular Mechanism And Clinical Significance Of FAM64A In The Development And Progression Of Renal Cell Carcinoma

Posted on:2021-02-26Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2404330611458229Subject:Surgery
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Purpose:Renal cell carcinoma is one of the most common tumors in the world,with its incidence accounting for 3-4% of all malignant tumors and about 90% of renal malignancies.Each year,it has more than 200 thousands new cases and 100 thousands deaths,seriously affecting human health.However,the clinical symptoms of early renal cancer are not obvious,20-30% of patients have already appeared distant metastasis of varying degrees at the time of diagnosis.To date,surgical treatment is the most effective treatment.However,30 to 40 percent of kidney cancers metastasize further after surgery.Some studies have suggested that the occurrence of renal cancer is related to genetic factors and environmental factors,but the molecular mechanism of the occurrence and development of renal cancer is still unclear.In recent years,the research on m TOR and the clinical application of targeted drugs make metastatic renal cancer remission,but it is difficult to achieve complete remission.Therefore,it is of great importance to study the molecular mechanism of the occurrence and development of renal cancer and look for markers for early diagnosis and prognosis estimation of renal cancer.Human FAM64 A gene is located on chromosome 17p13.2 and contains 8 exons.The human FAM64 A mRNA is 1517 bp long?NM001195228.1?,encoding a protein with 248 amino groups?np001182157.1?.Current studies showed that FAM64 A promoted cell proliferation by accelerating the cell cycle through G2/M phase.Current studies showed that FAM64 A was specifically highly expressed in a variety of tumor tissues,suggesting that FAM64 A may promote the occurrence and development of tumor cells as a proto oncogene.Therefore,we took FAM64 A and renal cancer as research objects to study the function of FAM64 A in the occurrence and development of renal cancer.To provide some theoretical basis for the targeted treatment of renal carcinoma in the future.Methods: qRT-PCR was used to detect the expression level of FAM64 A in 15 renal carcinoma tissues and their paired adjacent normal tissues.Select specific cell lines were knocked down and overexpressed FAM64 A,respectively,and the effect of FAM64 A on proliferation of renal cell lines was verified by cck-8 and Werstern blot.Cells at different stages were collected after synchronous cell cycle by thymoside double block method,and the changing trend of Cyclin B1 was detected by Werstern blot to determine the mechanism of FAM64 A in renal cancer cells.Finally,510 patients with renal cancer were selected by TCGA to analyze the relationship between the expression level of FAM64 A in renal cancer and the clinicopathological characteristics of the patients and the prognosis.Results: the expression level of FAM64 A in renal carcinoma was significantly higher and the difference was statistically significant?P<0.05?.The expression level of FAM64 A was also significantly higher than that of immortalized urothelial cells in renal cell lines.In 786-o cell lines,after the specific fam64a-sirna was transfected to down-regulate the expression of FAM64 A,the proliferation ability of 786-o cells was inhibited compared with the control group?P<0.05?,and the expression level of Cyclin B1 was down-regulated.In ACHN cell lines,after upregulation of the expression level of FAM64 A by lentivirus infection,compared with the control group,the proliferation ability of ACHN cells was enhanced?P<0.05?,and the expression level of Cyclin B1 was up-regulated.After 786-o cells were synchronized through cell cycle,and after fam64a-sirna was used to down-regulate FAM64 A,the cell entering G2/M phase was delayed compared with the control group.By analyzing the pathological characteristics of 510 patients and the expression of FAM64 A,it was found that the expression of FAM64 A was significantly correlated with the gender,tumor grade and the prognosis of the patients?P<0.05?,but not with the age of the patients?P>0.05?.Conclusion: FAM64 A is highly expressed in renal carcinoma tissues and renal carcinoma cell lines,and promotes tumor cell proliferation by accelerating tumor cells into G2/M phase.The expression of FAM64 A was significantly correlated with the gender,tumor grade and prognosis of renal cancer patients.
Keywords/Search Tags:FAM64A, Clear cell Renal cell carcinoma, Cyclin B1, Cell proliferation, Cell cycle
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