LAMA5 Regualtes Proliferation,Migration And Invasion Of Lung Adenocarcinoma By Targeting IQGAP2

Objectives:Lung cancer(LC)is one of the primary cancer types with the highest morbidity and mortality in the world.According to global cancer statistics,it is estimated that more than 2 million people are newly diagnosed with lung cancer each year.Lung adenocarcinoma(LUAD)is the most common type of lung cancer.Due to its late diagnosis and high heterogeneity,most lung cancers are diagnosed lately,and most of them are already in the advanced stage,which will bring huge benefits to patients and society.The pathogenesis of lung cancer is complex,and new pathogenesis of lung cancer remains to be explored.This study detected the mechanism of Laminin Subunit Alpha 5(LAMA5)on the proliferation,migration and invasion of lung adenocarcinoma,explored the molecular mechanism of its downstream signaling pathway,and provided a new target for the treatment of LUAD.Methods:1.Detect the expression levels of mRNA and protein in LAMA5 in the tissues of lung adenocarcinoma patients by real-time PCR and immunohistochemistry,and further statistically analyze the correlation between IHC results and clinical data such as age,sex,TNM stage and clinical stage of patients.2.We analyzed the expression difference of LAMA5 between lung adenocarcinoma and paracancerous tissue by bioinformatics(TCGA database),and analyzed the mutation of LAMA5 in lung adenocarcinoma.3.The LAMA5 gene was knocked out in the lung adenocarcinoma A549 cell line,and the cell phenotype experiments such as clone formation assay(Clone formation assay),scratch assay(Wound healing assay)and migration invasion assay(Transwell)were performed to clarify the expression of LAMA5.biological functions.4.Perform three-on-three transcriptome sequencing on lentiviral empty cells(NC)and LAMA5 knockout cells(LAMA5-KO),statistically analyze the transcriptome results,find related differential genes and perform GO/KEGG enrichment analysis,looking for LAMA5 downstream signaling molecular pathways,to provide new targets and strategies for the treatment of lung adenocarcinoma.Results:1.Compared with adjacent tissues,the expression of LAMA5 is up-regulated in lung adenocarcinoma tissue(mRNA level);LAMA5 is positively expressed in tumor tissue of LUAD patients(at the protein level),and LAMA5 is related to the T stage and clinical stage of the patient at the protein level,There is no correlation with age,sex,N stage,and M stage.2.Compared with the control group,the proliferation,migration and invasion of LAMA5-knockout A549 cells slowed down.3.IQGAP2 was upregulated at the mRNA level after LAMA5 knockout,consistent with the transcriptome results.Knockout of LAMA5 leads to high expression of tumor suppressor gene IQGAP2,which affects the occurrence and development of lung adenocarcinoma.Conclusion:The expression of LAMA5 is closely related to the occurrence of LUAD.LAMA5 can affect the occurrence and development of lung adenocarcinoma by affecting IQGAP2,which is expected to provide a new direction for the treatment of LUAD.