BACH1 Regulates The Migration And Invasion Of Lung Adenocarcinoma Through ITGA2

Purpose:Primary lung cancer is one of the most common tumors in the world and is the leading cause of tumor-related death.Lung adenocarcinoma is the most common pathological type.Although there are abundant therapeutic methods for lung adenocarcinoma,effective suppression of the mortality of lung adenocarcinoma still faces great challenges due to the occult onset and high metastasis of lung adenocarcinoma.Although the research on the occurrence and development of lung adenocarcinoma has been understood to some extent,the molecular mechanism of the formation and development of lung adenocarcinoma is not completely clear.Therefore,in-depth exploration of the molecular mechanism of the carcinogenesis and development of lung adenocarcinoma will help to discover important molecular targets and lay the foundation for new molecular diagnosis and targeted therapy of lung adenocarcinoma.As a member of the leucine zipper factor family,BACH1 is an important transcription factor that plays a key role in the regulation of reactive oxygen species production,cell cycle,heme homeostasis,hematopoiesis and immune production.Many studies have confirmed that BACH1 is significantly overexpressed in many human malignant tumors and plays an important role in promoting cancer.This study aims to further verify the relationship between the expression level of BACH1 in lung adenocarcinoma and clinicopathology,as well as its influence on lung adenocarcinoma and the potential mechanism.Method:(1)To explore the expression level of BACH1 in lung adenocarcinoma and its relationship with clinicopathological parameters by lung adenocarcinoma tissue microarray combined with bioinformatics.(2)H1975 and PC9 lung adenocarcinoma cell lines were used as the research object.The effects of BACH1 on the malignant progression and function of lung adenocarcinoma cells were explored by colony-forming assay,CCK-8 assay,cell scratch assay,Transwell assay,and nude mouse model of lung metastatic carcinoma.(3)The downstream pathways and target genes of BACH1 regulating lung adenocarcinoma cells were explored by bioinformatics and RNA-seq data analysis,qRT-PCR assay,WB assay,cell immunofluorescence assay and cell adhesion assay.(4)The relationship between BACH1 and its downstream target gene ITGA2 was explored by transcription factor correlation database analysis combined with ChIP-PCR and dual luciferase reporter gene assay.(5)The effects of ITGA2 on the migration,invasion and cytoskeleton of lung adenocarcinoma cells were explored by cell scratch assay,Transwell assay,cell immunofluorescence assay and cell adhesion assay.(6)BAHC1regulated the migration and invasion of lung adenocarcinoma cells and cytoskeleton-dependent and ITGA2 expression by recovery assay.Results:(1)BACH1 is abnormally high expressed in lung adenocarcinoma tissues,and the prognosis of patients with high expression is negatively correlated.(2)BACH1 promotes the migration and invasion ability of lung adenocarcinoma cells,but has no significant effect on the proliferation function of lung adenocarcinoma cells.(3)BACH1 promotes the migration and invasion of lung adenocarcinoma cells by participating in the regulation of F-actin cytoskeleton.(4)BACH1 directly binds to the upstream sequence of the ITGA2 promoter to promote its expression.(5)The BACH1-ITGA2 axis is involved in cytoskeleton regulation of lung adenocarcinoma cells by activating the FAK-RAC1-PAK signaling pathway.(6)ITGA2 is involved in cytoskeleton regulation of lung adenocarcinoma cells and promotes their migration and invasion.(7)The biological process of BACH1 promoting the migration and invasion of lung adenocarcinoma cells depends on the normal expression of ITGA2.Conclusion : In lung adenocarcinoma cells,BACH1 activates the FAK-RAC1-PAK signaling pathway to participate in the formation of tumor cytoskeleton by positively regulating the transcription expression of ITGA2,thus promoting the migration and invasion of tumor cells in lung adenocarcinoma cells.