不同肺转移潜能的大鼠肝癌细胞外泌体对巨噬细胞转录组的影响

doi:10.3969/j.issn.1672-5069.2021.03.003

Abstract

Abstract: Objective The aim of this study was to compare the effects of exosomes derived from rat liver cancer cells with different lung metastasis potentials on the transcriptome of macrophages.Methods The transcriptome sequencing technology was applied to compare the differences on transcriptome between macrophages stimulated by exosomes derived from two rat liver cancer cells (WB1 and WN1) with different lung metastasis potentials and to explore the potential mechanism of lung metastasis promoted by macrophages treated with exosomes. The KEGG pathway analysis, GO and protein protein interaction network analysis were performed on differentially expressed genes.Results There were 318 differentially expressed genes [log2(FC)≥1, P≤0.05] between the transcriptome of macrophages treated with exosomes derived from WN1 (liver cancer cells with high lung metastasis potential) and WB1(liver cancer cells with low lung metastasis potential), among which 296 being up-regulated and 22 down-regulated; the KEGG analysis found that up-regulated differential genes were mainly enriched in PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway and other inflammatory molecule-related signaling pathways as well as in cell adhesion-related signaling pathways; the GO analysis demonstrated that up-regulated differential genes were mainly enriched in terms of angiogenesis, epithelial-mesenchymal transition and metallopeptidase activity; furthermore, the hub genes screened by protein protein interaction network analysis, such as Vegfa, Il6 and Mmp3, were also located in the enrichment pathways mentioned above. Conclusion The transcriptome expression of macrophages stimulated by rat liver cancer cell exosomes with different lung metastasis potentials is significantly different. The exosomes derived from liver cancer cells with high lung metastasis potential might regulate multiple signaling pathways in macrophage to promote lung metastasis of tumor cells.

Key words: Hepatoma cells, Lung metastasis, Exosomes, Macrophages, Transcriptome sequencing, Bioinformatics analysis

Luo Weixin, Liu Chaoqun, Xu Leibo, et al. Effects of exosomes derived from rat liver cancer cells with different lung metastasis potentials on the transcriptome of macrophages[J]. Journal of Practical Hepatology, 2021, 24(3): 312-318.

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Effects of exosomes derived from rat liver cancer cells with different lung metastasis potentials on the transcriptome of macrophages

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