Bioinformatic analysis on differentially expressed genes in A549 cells exposed to silica dust / 中国职业医学

ABSTRACT

OBJECTIVE: To analyze the differentially expressed genes(DEGs), and screen the key genes and signaling pathways in human lung epithelial A549 cells exposed to silica dust using bioinformatics and gene chip. METHODS: The GSE30215 gene expression profiles of A549 cells exposed to silica dust were downloaded from Public Gene Expression Omnibus database developed by the National Center for Biotechnology Information. The DEGs were screened by using GEO2 R analysis tools. Then, the DEGs were imported into the biological information annotation database for Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The protein-protein interaction(PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes database and visualized using the software Cytoscape. Real-time quantitative polymerase chain reaction(PCR) was used to verify the expression of key DEGs in A549 cells. RESULTS: Of the 52 DEGs screened, 45 were up-regulated and 7 were down-regulated. The results of GO analysis showed that the DEGs were mainly distributed in extracellular region, associated with regulating biological functions such as chemotaxis, transcription factor activity and so on. KEGG pathway enrichment analysis showed that these DEGs were mainly involved in the tumor necrosis factor(TNF) signaling pathway and nucleotide-binding oligomerization domain like receptor signaling pathway. The top 10 key DEGs screened by PPI network were C-C motif chemokine ligand(CCL)2, prostaglandin-endoperoxide synthase 2, interleukin 6, C-X-C motif chemokine ligand(CXCL) 8, CXCL2, jun proto-oncogene, colony stimulating factor 2(CSF2), CCL20, TNF-α induced protein 3(TNFAIP3), and CXCL5. Real-time quantitative PCR results revealed that the changes of key genes were in consistent with the screening results, except the CCL2. CONCLUSION: We found 10 key DEGs that are related to the toxicity caused by exposure to silica dust in A549 cells by bioinformatics. Among them, CSF2, CCL20 and TNFAIP3 may provide new research direction for the mechanisms of the development of multiple pulmonary fibrotic diseases including pneumoconiosis.