The Expression Level And Role Of FOXG1 In Proliferation And Migration Of Lung Cancer

Objective:Lung cancer is a malignant tumor that originates from the bronchial mucosa or glands,and severely affects human life and health.In China,as one of the most common malignant tumors,the incidence and mortality of lung cancer have been increasing rapidly.In men,lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death.Due to the extremely aggressive nature of lung cancer,it has largely limited the therapeutic effects of various current treatment methods on lung cancer.Therefore,it’s becoming an active research field to develop new treatments and improve the therapeutic effects for lung cancer,which require the understanding of the pathogenesis and molecular mechanisms of lung cancer.FOXG1(Forkhead box G1),a member of the winged-helix forkhead family of transcription factors,is highly expressed in brain development and mainly involved in regulating the proliferation and differentiation of nerve cells.The abnormal expression of FOXG1 can cause neurological disorders,such as Lette Synthetic Symptoms,and other autism spectrum disorders.Recently,more and more researches focus on the role of FOXG1 in tumorigenesis.Previous studies have shown that the abnormal expression of FOXG1 was present in many tumors,e.g.glioblastoma,breast cancer,ovarian cancer,and hepatoblastoma,but the relationship between FOXG1 and lung cancer is still unclear.In our research,we firstly analyzed the expression and clinical significance of FOXG1 in lung cancer through databases and clinical specimens,and then investigated the role of FOXG1 in the proliferation,apoptosis,and migration of lung cancer cell.Our research provides a theoretical basis for elucidating the molecular mechanism of lung cancer.Methods:1 The expression and clinical significance of FOXG1 in different pathological types of lung cancer were analyzed by using TCGA and Oncomine databases.2 Analysis of FOXG1 expression in small cell lung cancer were carried out through immunohistochemical method.3 CCK8 assay was used to detect the effect of FOXG1 on the proliferation of lung cancer cells.4 Transwell assay and cell wound healing assay were used to study the effects of FOXG1 on the migration of lung cancer cells.5 Analysis of cell cycle and apoptosis were performed by using flow cytometry.6 The regulation of FOXG1 on the expression of p21WAF1/CIP1,proteins involeved in PI3K/AKT signaling pathway,and proteins involved in Epithelial-mesenchymal transition were analyzed through Western blot.Results:1 TCGA and Oncomine databases analysis showed that FOXG1 was highly expressed in lung adenocarcinoma,lung squamous carcinoma,and small cell lung cancer.Moreover,in lung adenocarcinoma,the recurrence-free survival of patients with higher FOXG1 expression was significantly decreased than that of patients with lower FOXG1 expression.2 Immunohistochemical analysis showed that FOXG1 was highly expressed in small cell lung cancer tissue compared to the pericarcinomatous tissue.3 CCK8 assay indicated that FOXG1 could promote the proliferation of lung cancer cells.4 Transwell assay revealed that FOXG1 could increase the migration ability of lung cancer cells,which was not detected when we performed cell wound healing assay.5 Cell cycle analysis showed that the number of lung cancer cells in S phase was significantly reduced when FOXG1 was overexpressed.Apoptosis analysis showed that overexpression of FOXG1 could reduce the apoptosis rates of lung cancer cells.6 Western blot analysis indicated that overexpression of FOXG1 could downregulate p21WAF1/CIP1 expression.In PI3K/AKT signaling pathway,expression of PTEN,p53,and BAX were all decreased,yet AKT was increased when FOXG1 was overexpressed.Meanwhile,we detected the upregulation of E-catenin,αE-catenin and vimentin,and downregulation of β-catenin and N-cadherin,which were involved in epithelial-mesenchymal transition.Conclusions:1 Database analysis suggested that the expression of FOXG1 in lung cancer tissues is higher than that in normal tissues.FOXG1 was highly expressed in small cell lung cancer tissue compared to the pericarcinomatous tissue.2 Overexpression of FOXG1 promoted the proliferation of lung cancer cell,through upregulation of cell cycle and inhibit of cell apoptosis.3 Overexpression of FOXG1 had a certain promotion effect on the migration of lung cancer cell.