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

实用肝脏病杂志 ›› 2021, Vol. 24 ›› Issue (3): 312-318.doi: 10.3969/j.issn.1672-5069.2021.03.003

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

罗伟鑫, 刘超群, 许磊波, 刘超, 吴文睿

510120 广州市中山大学孙逸仙纪念医院胆胰外科

收稿日期:2021-02-03 出版日期:2021-05-30 发布日期:2021-04-30
通讯作者: 吴文睿,E-mail:wuwr6@mail.sysu.edu.cn
作者简介:罗伟鑫,男,25岁,硕士研究生。E-mail:luowx3@mail2.sysu.edu.cn
基金资助:
国家自然科学基金资助项目(编号:81702904);中山大学青年教师培育基金资助项目(编号:19ykpy113)

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

Luo Weixin, Liu Chaoqun, Xu Leibo, et al

Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital,Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China

Received:2021-02-03 Online:2021-05-30 Published:2021-04-30

摘要/Abstract

摘要： 目的比较不同肺转移潜能的大鼠肝癌细胞来源外泌体对巨噬细胞转录组的影响。方法通过转录组测序技术,比较经两株不同肺转移潜能的大鼠肝癌细胞(WB1和WN1)来源外泌体处理的巨噬细胞的转录组差异,筛选差异基因并使用KEGG分析、GO分析和蛋白互作网络分析,探索癌细胞来源外泌体影响巨噬细胞功能促进肺转移的潜在机制。结果对比高肺转移肝癌细胞WN1和低肺转移肝癌细胞WB1来源外泌体处理的巨噬细胞转录组,存在318个差异表达基因【log2(差异倍数)≥1;P<0.05】,其中上调基因296个,下调基因22个;KEGG分析发现上调差异基因主要富集在PI3K-Akt信号通路、IL-17信号通路、TNF信号通路等炎症分子相关的信号通路和细胞黏附相关的信号通路上;GO分析发现上调差异基因主要富集在血管形成、上皮间质转化和金属肽酶活动等条目中;更进一步的蛋白质相互作用网络分析筛选得到的核心基因Vegfa、Il6和Mmp3等也位于上述富集通路中。结论巨噬细胞受不同肺转移潜能的大鼠肝癌细胞外泌体处理后,转录组存在显著性差异,高肺转移肝癌细胞来源外泌体可能通过调控巨噬细胞多个信号通路发挥促进肝癌肺转移的作用。

关键词: 肝癌细胞, 肺转移, 外泌体, 巨噬细胞, 转录组测序, 生物信息学分析

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

罗伟鑫, 刘超群, 许磊波, 刘超, 吴文睿. 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[J]. 实用肝脏病杂志, 2021, 24(3): 312-318.

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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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

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

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