Genomics study of human lung epithelial cells against new coronavirus SARS-CoV-2 infection / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 Based on the high-throughput sequencing data of the whole genome， genomics and bioinformatics analyses were made to analyze the gene expression changes in the epithelial cells of the lung tissue from patients with coronavirus disease 2019 （COVID-19）， and explore the effects of the new coronavirus SARS-CoV-2 on human lungs. This study can provide a theoretical basis for the exploration of SARS-CoV-2 on the pathogenesis of lung tissue. 【Methods】 The public data set GSE160435 was retrieved. The data were analyzed by Network analyst， Cytoscape 3.7.2， String 11.0， and other software. The differentially expressed genes were screened， gene function （Gene Ontology， GO） and signal pathway KEGG （Kyoto Encyclopedia of Genes and Genomes） enrichment analysis were carried out. We established the Protein-protein Interactions Network （PPI）， PPI of lung tissue-specific DEGs， DEG microRNA regulatory network， Transcription Factor （TF）-DEG regulatory network， and environmental chemicals DEGs regulatory network. 【Results】 We found 324 DEGs in the lung epithelial cells of patients with COVID-19， of which 112 （34.57%） were upregulated and 212 （65.43%） were downregulated. Enrichment analysis showed that DEGs were mainly involved in biological processes such as virus-related defense response， mainly involved in protein digestion and absorption， anti-human papillomavirus infection and other signaling pathways. Specific PPI network closely related to DEGs and lung tissue showed that PDGFRB and KIT were core proteins； hsa-mir-340 had targeted interaction with DEGs. It indicated that HOXB4， ISG15 and other related genes were regulated by transcription factors； DEGs interacted with environmental chemicals such as nickel and estradiol. 【Conclusion】 The gene expression pattern of lung epithelial cells in lung tissue of COVID-19 patients has changed significantly. Proteins or genes such as PDGFRB， MMP9 and KIT may play a vital role in the defense immunity of lung tissue. Micro-RNA， TF， signaling pathway molecules， environmental chemicals， and lung tissue-specific genes also play a role in the above-mentioned process. This study provides new ideas for exploring the pathogenic mechanism of SARS-CoV-2 on lung tissue and formulating clinical prevention， diagnosis and treatment measures.