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Study Of Target Gene, Chemotherapy Sensitivity And Clinical Prognosis On MicroRNA-195 In Gastric Carcinoma

Posted on:2016-03-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:J X LiFull Text:PDF
GTID:1224330464450658Subject:Oncology
Abstract/Summary:PDF Full Text Request
[Objective]Because of low diagnosis rate and few therapies, gastric cancer shows higher morbidity and mortalitythan other cancers. What’s more, some cancer markers such as CEA, CA724 display low specificity and sensitivity on diagnose. microRNA belongs to non-coding RNA with small molecule. It is similar to what oncogene or anti-oncogene regulates the tumorigenesis, development and prognosis.It demonstrated that microRNA-195 showed low expression in gastric cancer in our previous chip analysis. We believed that icroRNA-195 has nhibitory effect on tumor formation by acting on some target to active some proliferation pathway or apoptosis pathway. The finding of microRNA-195 may has a certain significance for early detection of gastric cancer and provide the theoretical basis on prognosis and recurrence risk.[Methods]To explore the correlation between gastric cancer and microRNA-195 experiment, we mainly do the following work:first, cells with different expression of microRNA-195 after transfection were extracted to RNA and reversed to cDNA and further verify the expression of microRNA-195 in human gastric cancer using Real-time PCR method; second, as we predicted, Akt3 is the target gene of microRNA-195. It is determined by dual luciferase report system, Western Blot and Real-time PCR; third, transfect cells, respectively, showed higher expression of microRNA-195 and negative control were analysis by flow cytometry on cell apoptosis and elaborated the function of invasion and migration by Transwell test and scratch test; fourth, cells in two groups with different expression of microRNA-195 showed cisplatin different sensitive with statistical significance; fifth, analysis of the clinical data of 29 patients were demonstrated the significance of tumor TNM stage, vascular invasion, Borrmann classification and the survival time in patients with different expression of microRNA-195.[Results]After all experiments, following results were showed that:first, the expression of microRNA-195 in gastric carcinoma showed down-regulation; second, Akt3 was the target gene of microRNA-195 which was reduced in cells with overexpressing microRNA-195; third, the experiments shows that the invasive ability of cells were decreased and early apoptosis were increased in over expression of microRNA-195.; fourth, the high expression of microRNA-195 showed chemosensitivity after using cispltin; fifth, PFS and OS was significantly prolonged in patients with overexpressing microRNA-195 has statistical significance (P<0.05).[Conclusion]microRNA-195 in patients with gastric cancer showed down-regulation and overexpression of microRNA-195 showed significantly inhibitory effect on cancer. It plays role on targeting gene of Akt3.
Keywords/Search Tags:microRNA-195, gastric cancer, Akt3, chemothepy sensitivity, survival
PDF Full Text Request
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