The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer
Fusobacterium nucleatum is strongly linked to colorectal cancer (CRC) progression, but its mechanisms for influencing macrophage polarization and tumor development are not well understood. We established an in vitro model of F. nucleatum infection in RAW264.7 macrophages to investigate these process...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549564/full |
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| author | Wei Zheng Wei Zheng Yuxin Wang Yuxin Wang Haoyang Sun Haoyang Sun Surina Bao Surina Bao Shuai Ge Shuai Ge Chunshan Quan Chunshan Quan |
| author_facet | Wei Zheng Wei Zheng Yuxin Wang Yuxin Wang Haoyang Sun Haoyang Sun Surina Bao Surina Bao Shuai Ge Shuai Ge Chunshan Quan Chunshan Quan |
| author_sort | Wei Zheng |
| collection | DOAJ |
| description | Fusobacterium nucleatum is strongly linked to colorectal cancer (CRC) progression, but its mechanisms for influencing macrophage polarization and tumor development are not well understood. We established an in vitro model of F. nucleatum infection in RAW264.7 macrophages to investigate these processes. Macrophage polarization was evaluated using scanning electron microscopy (SEM), real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. RNA sequencing (RNA-Seq) identified differentially expressed genes (DEGs) and enriched pathways, focusing on the role of the NF-κB signaling pathway in macrophage polarization. F. nucleatum infection induced M2 polarization in RAW264.7 macrophages, as confirmed by SEM analysis and RT-qPCR validation. A total of 2,029 DEGs were identified after F. nucleatum infection, with 763 upregulated and 1,266 downregulated. GO and KEGG enrichment analysis showed that cytokine-cytokine receptor interaction, TNF signaling, and NF-κB signaling pathways are upregulated in macrophages after F. nucleatum infection, indicating enhanced cytokine activity and immune response. Key genes (Nfkb1, Nfkb2, Malt, Lta, Ltb, Tnf) and proteins (P50, P100) in the NF-κB pathway are upregulated, indicating the crucial role of the NF-κB pathway in M2 macrophage polarization. This study offers crucial evidence regarding the role of the NF-κB signaling pathway in modulating F. nucleatum-induced macrophage M2 polarization, underscoring its significance in the progression of colorectal cancer. |
| format | Article |
| id | doaj-art-220b03d2c8764a23b5e15aee5b5d7300 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-220b03d2c8764a23b5e15aee5b5d73002025-08-20T01:51:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15495641549564The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancerWei Zheng0Wei Zheng1Yuxin Wang2Yuxin Wang3Haoyang Sun4Haoyang Sun5Surina Bao6Surina Bao7Shuai Ge8Shuai Ge9Chunshan Quan10Chunshan Quan11Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, ChinaDepartment of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, Liaoning, ChinaKey Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, ChinaDepartment of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, Liaoning, ChinaKey Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, ChinaDepartment of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, Liaoning, ChinaKey Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, ChinaDepartment of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, Liaoning, ChinaKey Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, ChinaDepartment of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, Liaoning, ChinaKey Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, ChinaDepartment of Bioengineering, College of Life Science, Dalian Minzu University, Dalian, Liaoning, ChinaFusobacterium nucleatum is strongly linked to colorectal cancer (CRC) progression, but its mechanisms for influencing macrophage polarization and tumor development are not well understood. We established an in vitro model of F. nucleatum infection in RAW264.7 macrophages to investigate these processes. Macrophage polarization was evaluated using scanning electron microscopy (SEM), real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. RNA sequencing (RNA-Seq) identified differentially expressed genes (DEGs) and enriched pathways, focusing on the role of the NF-κB signaling pathway in macrophage polarization. F. nucleatum infection induced M2 polarization in RAW264.7 macrophages, as confirmed by SEM analysis and RT-qPCR validation. A total of 2,029 DEGs were identified after F. nucleatum infection, with 763 upregulated and 1,266 downregulated. GO and KEGG enrichment analysis showed that cytokine-cytokine receptor interaction, TNF signaling, and NF-κB signaling pathways are upregulated in macrophages after F. nucleatum infection, indicating enhanced cytokine activity and immune response. Key genes (Nfkb1, Nfkb2, Malt, Lta, Ltb, Tnf) and proteins (P50, P100) in the NF-κB pathway are upregulated, indicating the crucial role of the NF-κB pathway in M2 macrophage polarization. This study offers crucial evidence regarding the role of the NF-κB signaling pathway in modulating F. nucleatum-induced macrophage M2 polarization, underscoring its significance in the progression of colorectal cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549564/fullFusobacterium nucleatumcolorectal cancermacrophage polarizationNF-κB signaling pathwaytrascriptome |
| spellingShingle | Wei Zheng Wei Zheng Yuxin Wang Yuxin Wang Haoyang Sun Haoyang Sun Surina Bao Surina Bao Shuai Ge Shuai Ge Chunshan Quan Chunshan Quan The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer Frontiers in Immunology Fusobacterium nucleatum colorectal cancer macrophage polarization NF-κB signaling pathway trascriptome |
| title | The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer |
| title_full | The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer |
| title_fullStr | The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer |
| title_full_unstemmed | The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer |
| title_short | The role of Fusobacterium nucleatum in macrophage M2 polarization and NF-κB pathway activation in colorectal cancer |
| title_sort | role of fusobacterium nucleatum in macrophage m2 polarization and nf κb pathway activation in colorectal cancer |
| topic | Fusobacterium nucleatum colorectal cancer macrophage polarization NF-κB signaling pathway trascriptome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1549564/full |
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