Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer.
Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer.
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DOI：
10.1016/j.csbj.2023.06.010
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发表时间：
2023
影响因子：
6
通讯作者：
Wang, Min
中科院分区：
文献类型：
--
作者：
Chen, Zimei;Yang, Ke;Zhang, Jiayi;Ren, Shufan;Chen, Hui;Guo, Jiahui;Cui, Yizhi;Wang, Tong;Wang, Min
关键词：
HIV-1 相关结直肠癌 (HA-CRC) 是研究最充分的非艾滋病定义癌症之一。在本研究中，我们通过数据独立的采集质谱 (MS) 分析了 HA-CRC 和配对远端组织 (HA-RT) 的蛋白质组。定量的蛋白质可以根据 PCA 或聚类分析区分 HA-CRC 和 HA-RT 组。作为背景比较，我们重新分析了 CPTAC 发布的非 HIV-1 感染 CRC（非 HA-CRC）的 MS 数据。根据 GSEA 结果，我们发现 HA-CRC 和非 HA-CRC 具有类似的过度代表性 KEGG 通路。霍尔马克分析表明，抗病毒反应的条件仅在 HA-CRC 中显着丰富。网络和分子系统分析集中了 IFN 相关抗病毒反应和癌症途径的串扰，这受到 HA-CRC 组织中检测到的 ISGylated 蛋白显着上调的支持。我们进一步证明，以8E5细胞为代表的有缺陷的HIV-1储存细胞可以通过细胞外囊泡（EV）携带的细胞相关HIV-1 RNA（CA-HIV RNA）的水平转移来激活人类巨噬细胞中的IFN途径。总之，分泌的 HIV-1 储存细胞和含有 CA-HIV RNA 的 EV 可以诱导巨噬细胞中的 IFN 通路激活，这有助于解释 HA-CRC 中抗病毒反应和癌性通路之间的系统串扰的机制之一。
HIV-1 associated colorectal cancer (HA-CRC) is one of the most understudied non-AIDS-defining cancers. In this study, we analyzed the proteome of HA-CRC and the paired remote tissues (HA-RT) through data-independent acquisition mass spectrometry (MS). The quantified proteins could differentiate the HA-CRC and HA-RT groups per PCA or cluster analyses. As a background comparison, we reanalyzed the MS data of non-HIV-1 infected CRC (non-HA-CRC) published by CPTAC. According to the GSEA results, we found that HA-CRC and non-HA-CRC shared similarly over-represented KEGG pathways. Hallmark analysis suggested that terms of antiviral response were only significantly enriched in HA-CRC. The network and molecular system analysis centered the crosstalk of IFN-associated antiviral response and cancerous pathways, which was favored by significant up-regulation of ISGylated proteins as detected in the HA-CRC tissues. We further proved that defective HIV-1 reservoir cells as represented by the 8E5 cells could activate the IFN pathway in human macrophages via horizonal transfer of cell-associated HIV-1 RNA (CA-HIV RNA) carried by extracellular vesicles (EVs). In conclusion, HIV-1 reservoir cells secreted and CA-HIV RNA-containing EVs can induce IFN pathway activation in macrophages that contributes to one of the mechanistic explanations of the systems crosstalk between antiviral response and cancerous pathways in HA-CRC.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1609057113
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影响因子：
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影响因子：
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Janjua NZ