Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer

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...

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Main Authors: Zimei Chen, Ke Yang, Jiayi Zhang, Shufan Ren, Hui Chen, Jiahui Guo, Yizhi Cui, Tong Wang, Min Wang
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037023002234
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author Zimei Chen
Ke Yang
Jiayi Zhang
Shufan Ren
Hui Chen
Jiahui Guo
Yizhi Cui
Tong Wang
Min Wang
author_facet Zimei Chen
Ke Yang
Jiayi Zhang
Shufan Ren
Hui Chen
Jiahui Guo
Yizhi Cui
Tong Wang
Min Wang
author_sort Zimei Chen
collection DOAJ
description 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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spelling doaj.art-bc9bc9e5053142b39da9910a945581592023-12-21T07:31:40ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012133693382Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancerZimei Chen0Ke Yang1Jiayi Zhang2Shufan Ren3Hui Chen4Jiahui Guo5Yizhi Cui6Tong Wang7Min Wang8The First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China; Department of Infectious Diseases, Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, Hunan 410005, ChinaDepartment of Infectious Diseases, Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, Hunan 410005, ChinaThe First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, ChinaThe First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, ChinaDepartment of Infectious Diseases, Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, Hunan 410005, ChinaThe First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, ChinaThe First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, ChinaThe First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China; Department of Infectious Diseases, Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, Hunan 410005, China; Corresponding author at: The First Affiliated Hospital, MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.Department of Infectious Diseases, Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, Hunan 410005, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2001037023002234HIV-1-associated colorectal cancerProteomicsHIV-1 reservoirExtracellular vesiclesIFN pathwayCell-associated HIV-1 RNA
spellingShingle Zimei Chen
Ke Yang
Jiayi Zhang
Shufan Ren
Hui Chen
Jiahui Guo
Yizhi Cui
Tong Wang
Min Wang
Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer
Computational and Structural Biotechnology Journal
HIV-1-associated colorectal cancer
Proteomics
HIV-1 reservoir
Extracellular vesicles
IFN pathway
Cell-associated HIV-1 RNA
title Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer
title_full Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer
title_fullStr Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer
title_full_unstemmed Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer
title_short Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer
title_sort systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in hiv 1 associated colorectal cancer
topic HIV-1-associated colorectal cancer
Proteomics
HIV-1 reservoir
Extracellular vesicles
IFN pathway
Cell-associated HIV-1 RNA
url http://www.sciencedirect.com/science/article/pii/S2001037023002234
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