Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition
Abstract Background The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum (F. nucleatum, FN) being found in high abundance in colorectal cancer tissues. Previous research has emphasized the significant role of F. nucl...
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2025-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-024-01097-4 |
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| author | Yulong Yu Han Yin Bili Wu Weiheng Zhao Yuan Wang Aifeina Aili Mu Yang Qianqian Yu Xianglin Yuan |
| author_facet | Yulong Yu Han Yin Bili Wu Weiheng Zhao Yuan Wang Aifeina Aili Mu Yang Qianqian Yu Xianglin Yuan |
| author_sort | Yulong Yu |
| collection | DOAJ |
| description | Abstract Background The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum (F. nucleatum, FN) being found in high abundance in colorectal cancer tissues. Previous research has emphasized the significant role of F. nucleatum in the occurrence of CRC. However, the impact of F. nucleatum on CRC liver metastasis has not been well understood. Methods The effects of F. nucleatum on metastasis ability of CRC cell were evaluated in vitro were examined by wound-healing assay and transwell assay. The mouse model of CRC liver metastasis was constructed by spleen injection, and the degree of liver metastasis was assessed by in vivo bioluminescence imaging. The gene expression changes in CRC cells after co-culture with F. nucleatum was analyzed through transcriptome sequencing. qRT-PCR and Western Blot assays were performed to validate the expression of related genes and proteins. Results The metastasis ability of CRC cells was significantly enhanced after co-culture with F. nucleatum in vitro. In the mouse model, F. nucleatum also promoted the development of liver metastasis in CRC. Mechanistically, F. nucleatum infection increased the expression of IL-8 by downregulated the level of miR-5692a, a regulatory microRNA of IL-8. This led to the activation of the ERK pathway and resulted in the epithelial-mesenchymal transition (EMT) of CRC cells. Conclusions Our results suggest that F. nucleatum promotes CRC liver metastasis by inducing epithelial-mesenchymal transition through the miR-5692a/IL-8 axis. These findings provide new insights for the prevention and treatment of colorectal cancer liver metastasis. |
| format | Article |
| id | doaj-art-4443568528724365bcd4cb7164f790ee |
| institution | Kabale University |
| issn | 1423-0127 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj-art-4443568528724365bcd4cb7164f790ee2025-01-12T12:34:07ZengBMCJournal of Biomedical Science1423-01272025-01-0132111510.1186/s12929-024-01097-4Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transitionYulong Yu0Han Yin1Bili Wu2Weiheng Zhao3Yuan Wang4Aifeina Aili5Mu Yang6Qianqian Yu7Xianglin Yuan8Department of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital,Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum (F. nucleatum, FN) being found in high abundance in colorectal cancer tissues. Previous research has emphasized the significant role of F. nucleatum in the occurrence of CRC. However, the impact of F. nucleatum on CRC liver metastasis has not been well understood. Methods The effects of F. nucleatum on metastasis ability of CRC cell were evaluated in vitro were examined by wound-healing assay and transwell assay. The mouse model of CRC liver metastasis was constructed by spleen injection, and the degree of liver metastasis was assessed by in vivo bioluminescence imaging. The gene expression changes in CRC cells after co-culture with F. nucleatum was analyzed through transcriptome sequencing. qRT-PCR and Western Blot assays were performed to validate the expression of related genes and proteins. Results The metastasis ability of CRC cells was significantly enhanced after co-culture with F. nucleatum in vitro. In the mouse model, F. nucleatum also promoted the development of liver metastasis in CRC. Mechanistically, F. nucleatum infection increased the expression of IL-8 by downregulated the level of miR-5692a, a regulatory microRNA of IL-8. This led to the activation of the ERK pathway and resulted in the epithelial-mesenchymal transition (EMT) of CRC cells. Conclusions Our results suggest that F. nucleatum promotes CRC liver metastasis by inducing epithelial-mesenchymal transition through the miR-5692a/IL-8 axis. These findings provide new insights for the prevention and treatment of colorectal cancer liver metastasis.https://doi.org/10.1186/s12929-024-01097-4Colorectal cancerFusobacterium nucleatumMetastasisIL-8MicroRNA |
| spellingShingle | Yulong Yu Han Yin Bili Wu Weiheng Zhao Yuan Wang Aifeina Aili Mu Yang Qianqian Yu Xianglin Yuan Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition Journal of Biomedical Science Colorectal cancer Fusobacterium nucleatum Metastasis IL-8 MicroRNA |
| title | Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition |
| title_full | Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition |
| title_fullStr | Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition |
| title_full_unstemmed | Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition |
| title_short | Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition |
| title_sort | fusobacterium nucleatum promotes colorectal cancer liver metastasis via mir 5692a il 8 axis by inducing epithelial mesenchymal transition |
| topic | Colorectal cancer Fusobacterium nucleatum Metastasis IL-8 MicroRNA |
| url | https://doi.org/10.1186/s12929-024-01097-4 |
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