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Regulation Of MiR - 34a On Invasion And Invasion Of Gastric Cancer Cells And Related Factors Of Clinical Prognosis In Gastric Cancer

Posted on:2016-08-03Degree:MasterType:Thesis
Country:ChinaCandidate:Y P DuFull Text:PDF
GTID:2134330461993290Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objetives: To explore the expression of mi R-34 a in two gastric cancer cell lines with different ability of migration and invasion and investigate the biological effects of mi R-34 a in gastric cancer.Methods: The expression level of mi R-34 a in 2 human gastric cell lines(SGC-7901 and BCG-823) was examined by real-time polymerase chain reaction(RT-PCR). Woud healing assay, Transwell assay and CCK8 test were performed to explore the effect of mi R-34 a on migration, invasion and proliferation of gastric cancer(GC) cell lines. Bioinformatics and Dual luciferase experiment were performed to investigate the potential target gene. The Fra-1, MMP9, Cyciln D1 protein level was analyzed by Western blotting.Results: Expression level of mi R-34 a was lower in SGC-7901 than BCG-823 which showed weaker ability of migration and invasion. Ectopic expression of mi R-34 a significantly suppressed migration, invasion and proliferation of SGC7901 and BCG823. The luciferase reporter assays revealed that Fra-1was a direct target gene of mi R-34 a. And Fra-1 could reduce the expression of downstream molecular matrix metalloproteinases(MMP-9) and Cyclin D1.Conclusions: Ectopic expression of mi R-34 a could inhibit migration, invasion and proliferation of GC cell lines through or partly via regulating the target gene Fra-1 and its downstream molecular MMP-9 and Cyclin D1.Recently, lymphocyte to monocyte ratio(LMR) has been reported to be associated with clinical outcomes in some types of cancer but has not been explored in gastric cancer. In this study, we analyzed the association between LMR and clinical outcomes in stage II /III gastric cancer patients. Preoperative LMR calculated from peripheral lymphocyte and monocyte with corresponding clinical features from 426 stage II /III gastric cancer patients were noted. Kaplan–Meier method and Cox regression model were applied for overall survival(OS) and recurrence-free survival(RFS). Related with smaller tumor size(P<0.001), increased LMR could predict better OS(hazard ratio(HR), 0.688; 95% confidence interval(CI), 0.521-0.908; P = 0.008) and was borderline significantly associated with better RFS(HR, 0.775; 95% CI, 0.592-1.01; P = 0.06) in stage II /III gastric cancer patients through multivariable analysis. Subgroup analyses revealed that except stage III patients for RFS which yielded borderline significance(P=0.052), lower LMR was associated with poor clinical outcomes for patients regardless of different stages or whether the patients received adjuvant chemotherapy. The elevated preoperative LMR level was a significant favorable factor in the prognosis of stage II /III gastric cancer patients, especially for those with stage II. However, further validation of our findings is warranted.
Keywords/Search Tags:gastric cancer, mi R-34a, invasion, migration, Fra-1, LMR, prognosis
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