The Study Of Rac3 Molecular Mechanism Through ERK Signaling Pathway In Lung Adenocarcinoma

Background: Lung cancer is the malignant tumor with the highest morbidity and mortality in the world,and its main pathological type is lung adenocarcinoma.In the previous experiments of our research group,Rac3 was first screened and identified as a possible new driver gene for lung adenocarcinoma.Rac3 is a member of the Rho family Rac subfamily,which plays an useful role in a variety of human tumors.On the basis of existing studies,finding out the relationship between Rac3 gene and prognosis of lung adenocarcinoma,the role of Rac3 in the proliferation and migration of lung adenocarcinoma cells,and the mechanism of Rac3 in promoting the proliferation and migration of lung adenocarcinoma cells are of great significance.Methods: 1.542 patients with lung adenocarcinoma in the TCGA database were selected for analysis,the expression of Rac3 in cancer tissues and normal lung tissues were compared.Plotter database was selected to analyze the relationship between Rac3 expression and 5-year overall survival rate of patients by Kaplan-Meier method.2.Human lung adenocarcinoma cell lines A549 and H1299 were used to build Rac3 knockdown and high-expression cell lines.The role of Rac3 in the proliferation and migration of lung adenocarcinoma cells was detected by cell proliferation and healing-wound test.3.The Rac3 knockdown cell lines were used to detect the changes of intracellular signaling pathways by serum starvation test and Western Blot experiment,screening out the signaling pathways with significant differences and study the biological function of them.Results: 1.The results of TCGA database result showed that Rac3 expression in 542 patients with lung adenocarcinoma was significantly higher than that in normal lung tissues,and the result is statistically significant(P<0.01).Kaplan-Meier survival analysis showed that patients with high Rac3 level had a significantly shorter 5-year overall survival(P<0.0001).2.In A549 and H1299 cell lines,Rac3 shRNA is used to build Rac3 knockdown and high expression cell lines by lentivirus infection.The proliferation and migration of lung adenocarcinoma cells were detected by cell proliferation test and healing-wound test.By control group,the proliferation and migration rate of Rac3-sh RNA group was significantly decreased,while that of Rac3 high expression group was significantly increased(P < 0.01).3.Serum starvation test and Western Blot results showed that in A549 cell lines,the phosphorylation of ERK pathway was significantly reduced after Rac3 expression was knocked down by sh RNA compared with the control group.Conclusion: 1.Rac3 is highly expressed in lung adenocarcinoma.2.The overall survival(OS)of patients with high Rac3 expression was significantly shorter than that of patients with low Rac3 expression.3.Rac3 promotes the proliferation of lung adenocarcinoma cells.4.Rac3 promotes the migration of lung adenocarcinoma cells.5.Rac3 probably regulates the ERK signaling pathway to promote the proliferation in lung adenocarcinoma cells.