Exploring The Immune Regulation Mechanism Of C-MET Expression In Non-small Cell Lung Cancer Based On Transcriptome Sequencing

Background:C-MET is a proto oncogene encoding receptor tyrosine kinase receptor,which is involved in tumor formation,metastasis,invasion and regulation of immune microenvironment,but the specific regulatory mechanism is not clear.In this study,we analyzed the immunoregulation mechanism of C-MET expression in non-small cell lung cancer by transcriptome sequencing technology.Methods:First,we selected the lung adenocarcinoma cell line with high C-MET expression(H1993)and the lung squamous cell carcinoma cell line(EBC-1)as the research objects,and used si RNA molecular interference technology to construct the low C-MET expression cell model.Then,we used RNA sequencing technology to sequence the transcriptome of the cell model before and after interference,and then analyzed the differential expression of the sequencing results.The analysis methods include Gene Ontology(GO)enrichment analysis Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis;Preliminary screening of relevant regulatory pathways and biological functions of C-MET;At the same time,miRNA measurement and differential expression analysis were conducted on the cell model before and after interference.Two software,miRanda and RNAhybrid,were used to predict the target genes of miRNA.The C-MET molecular interaction network of miRNA target genes constructed by STRING was used to preliminarily explore the relevant regulatory pathways and biological functions involved in differential miRNA target genes.Finally,the co culture technique of human immune cells with H1993 and EBC-1 was used to verify the effect of C-MET on the secretion of immune factors(INF)by immune cells-γ、 INF-β、 The impact of CXCL-10.Results1.There are 38 differentially expressed genes in the group with differentially expressed genes before and after c-Met regulation of H1993,and 467 differentially expressed genes in the group with differentially expressed genes before and after c-Met regulation of EBC-1.There were 15 differentially expressed miRNAs in the group with differentially expressed H1993 before and after c-Met regulation,and 36 differentially expressed miRNAs in the group with differentially expressed EBC-1before and after c-Met regulation.2.KEGG analysis of differential genes suggests that C-MET expression may participate in the regulation of immune cell regulatory factors through the IL-17 signaling pathway,white blood cell differentiation,cytokine receptor activity,cell cycle,cytokine receptor activity,and cytokine cytokine receptor interaction..3.KEGG analysis of miRNA target genes showed that C-MET expression participated in the regulation of immune cell regulators through chemokine signaling pathway,abnormal transcriptional regulation pathway in cancer,cell adhesion molecule,and Th17 cell differentiation.4.Co culture experiments with PBMC cells showed that high expression of C-MET promotes immune regulatory factor INF-γ、 INF-β High m RNA expression of.ConclusionC-MET expression may participate in the regulation of tumor surrounding immune microenvironment through IL-17 signaling pathway,leukocyte differentiation,cytokine receptor activity;The specific genes involved in the immune microenvironment are IL1 B,JUND,FOS,CXCL8,HSP90AA1,FOSL1,CSF2,S100A9,and the immune regulatory factor INF-γ、 INF-β 、 Regulation of CXCL-10.