新型冠状病毒(SARS-COV-2)感染后人嗅觉神经上皮细胞的基因组调控网络研究

Genomic regulatory network of human olfactory neuroepithelial cells infected with novel coronavirus(SARS-COV-2)

目的·探索新型冠状病毒(SARS-COV-2)感染人体后,人嗅觉神经上皮细胞的基因组学变化,建立差异表达基因(differentially expressed genes,DEGs)的蛋白互作(protein-protein interactions,PPI)网络等,了解SARS-COV-2感染对人嗅觉神经上皮细胞的影响,为新型冠状病毒肺炎的防治提供参考依据。方法·采用NetworkAnalyst分析公共数据集GSE151973,挑选DEGs,进行基因本体(Gene Ontology, GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路分析,创建PPI网络、DEGs-microRNA调控网络、转录因子-DEGs调控网络、环境化学物-DEGs调控网络以及药物-DEGs调控网络,使用Cytoscape 3.7.2进行图视化。结果·SAR-COV-2侵袭人嗅觉神经上皮细胞后,基因表达谱部分发生明显上调或下调,共发现了568个DEGs,其中上调基因550个(96.8%),下调基因18个(3.2%);通过富集分析,DEGs主要参与鼻呼吸和嗅觉上皮的内皮发育、血管生成等生物学过程,N端肉豆蔻酰化结构域结合等分子功能表达。PPI网络提示RTP1和RTP2为核心蛋白;MAZ为最具有影响效应的转录因子;Hsa-mir-26b-5p对DEGs的调控作用最明显;环境化学物丙戊酸钠对DEG最具影响;药物乙醇对DEGs的调控最具有影响。结论·感染SAR-COV-2后嗅觉神经上皮细胞基因表达明显改变,SARS-CoV-2可能通过抑制PAX7功能来抑制肌肉卫星细胞的增殖分化。RTP1、RTP2可能通过促嗅觉受体上膜的能力以及其对气味配体反应性抵抗SARS-CoV-2,MAZ可能通过影响细胞的生长、增殖调控DEGs;microRNA、环境化学物和药物在人嗅觉神经上皮细胞抗SAR-COV-2感染过程中也发挥着不可忽视的作用。

Objective To explore the genomic changes of human olfactory neuroepithelial cells after the novel coronavirus(SARS-COV-2) infecting the human body, and establish a protein-protein interaction(PPI) network of differentially expressed genes(DEGs), in order to understand the impact of SARS-COV-2 infection on human olfactory neuroepithelial cells, and provide reference for the prevention and treatment of new coronavirus pneumonia. Methods The public dataset GSE151973 was analyzed by NetworkAnalyst. DEGs were selected by conducting Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) signal pathway analysis. PPI network, DEGs-microRNA regulatory network, transcription factor-DEGs regulatory network,environmental chemicals-DEGs regulatory network, and drug-DEGs regulatory network were created and visualized by using Cytoscape 3.7.2. Results After SAR-COV-2 invading human olfactory neuroepithelial cells, part of the gene expression profile was significantly up-regulated or down-regulated. A total of 568 DEGs were found, including 550 up-regulated genes(96.8%) and18 down-regulated genes(3.2%). DEGs were mainly involved in biological processes such as endothelial development and angiogenesis of the olfactory epithelium, and the expression of molecular functions such as the binding of the N-terminal myristylation domain. PPI network suggested that RTP1 and RTP2 were core proteins. MAZ was the most influential transcription factor. Hsa-mir-26b-5p had the most obvious interaction with DEGs regulation. Environmental chemical valproic acid and drug ethanol had the most influence on the regulation of DEG. Conclusion The gene expression of olfactory neuroepithelial cells is significantly up-regulated or down-regulated after infection with SAR-COV-2. SARS-CoV-2 may inhibit the proliferation and differentiation of muscle satellite cells by inhibiting the function of PAX7. RTP1 and RTP2 may resist SARS-CoV-2 by promoting the ability of olfactory receptors to coat the membrane and enhancing the ability of olfactory receptors to respond to odorant ligands.MAZ may regulate DEGs by affecting cell growth and proliferation. Micro RNA, environmental chemicals and drugs also play an important role in the anti-SAR-COV-2 infection process of human olfactory neuroepithelial cells.