Correlation Between MEF2C In Exosomes And Colorectal Cancer Progression

Background:Exosomes are bioactive extracellular vesicles with a diameter between 40 and 130 nm,which can carry a variety of biologically active components and play a key role in regulating tumor occurrence,development,and drug resistance.The aim of this study was to explore the effect of the transcription factor MEF2C in exosomes on the progression of colorectal cancer.Materials and method:We downloaded the mRNA-seq datasets from the Gene Expression Omnibus(GEO),the Cancer Genome Atlas(TCGA)and exoRBase database,and applied the limma software package to analyze the differential genes in colorectal cancer tissues and exosomes.At the same time,the relevant clinical information in the TCGA database was downloaded,including the clinical follow-up information of 375 colorectal cancer patients.The GSE32323 and GSE110224 datasets in GEO Data(both datasets each contain 17 pairs of colorectal cancer samples)were downloaded for pairwise analysis of differential genes.exosome-related data of colorectal cancer can be extracted from the exoRBase dataset,including 32 normal samples and 12 colorectal cancer samples,for analyzing the expression of differential genes in exosomes.The differential genes were clustered by the WGCNA software package,and the association modules were determined according to the Pearson correlation coefficient.The key modules related to colorectal cancer were found in WGCNA.Further,key genes associated with colorectal cancer were searched in key modules.The gene expression associated with MEF2C was explored by Pearson correlation test.Gene function and pathway clustering of MEF2C related Genes were performed by GO and KEGG analysis.Furthermore,qPCR and immunohistochemistry staining were used to verify MEF2C and CD36 expression in CRC tissues.The biological function of the MEF2C was explored by performing proliferation,migration and invasion assays.In terms of mechanism,Chip experiment was used to reveal CD36 transcription regulated by exosomal MEF2C.Results:In this study,differential gene analysis was performed on the TCGA,GEO and exoRBase datasets,and 3481 differential genes were found in the TCGA dataset,5466 differential genes in the GEO dataset,and 129 differential genes in the exosome dataset.WGCNA analysis was performed on the TCGA and GEO datasets,and the yellow modules were found to be associated with colorectal cancer in the TCGA dataset,and the brown modules were associated with colorectal cancer in the GEO dataset.Then,the differential genes in the yellow module,the differential genes in the brown module and the differential genes in the exosome data were joint analyzed to find the key genes that were differentially expressed in colorectal cancer tissues and exosomes.Further,through correlation analysis,it was found that 609 genes were significantly correlated with the expression of MEF2C.Modular analysis of 609 potential genes was performed using WGCNA software package to find target genes related to MEF2C and colorectal cancer,and found that the genes in the turquoise module were closely related to colorectal cancer.Kaplan-Meier analyses of turquoise module showed that CD36 was closely related to the overall survival(OS)of CRC patients.Therefore,we selected CD36 as the target gene of MEF2C for relevant experimental verification.There were obvious differences in the expression levels of exosomal MEF2C and CD3 6 in CRC and normal tissues according to quantitative PCR and immunohistochemical assays.The results of colony formation assay showed that overexpression of MEF2C inhibited the proliferation ability of SW620 cells.Cell migration and invasion assay showed that MEF2C overexpression inhibited the migration and invasion abilities of SW620 cells.Chip experiments showed that MEF2C could regulate CD36 transcription.ConclusionIn this study,we found that MEF2C in exosomes has an important tumor suppressor role in colorectal cancer by bioinformatics methods,and verified that MEF2C can regulate the progression of colorectal cancer by regulating the transcription of CD36.Exosomal MEF2C is a well molecule in colorectal cancer that may serve as a potential biomarker and may be potential therapeutic in colorectal cancer.