CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment
Background: Colony-stimulating factor 3 (CSF3) is a cytokine that promotes inflammation by stimulating the maturation, proliferation, and trafficking of myeloid progenitor cells. However, the functional importance of CSF3 in colorectal cancer (CRC) remains unclear. Methods: CSF3 expression levels in...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000415 |
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| author | Junfeng Xu Na Li Hui Xie Changwei Duan Xingchen Liao Ruoran Li Heng Zhang Yuanming Pan Xianzong Ma Shuwen Du Jianqiu Sheng Xin Wang Lang Yang Peng Jin |
| author_facet | Junfeng Xu Na Li Hui Xie Changwei Duan Xingchen Liao Ruoran Li Heng Zhang Yuanming Pan Xianzong Ma Shuwen Du Jianqiu Sheng Xin Wang Lang Yang Peng Jin |
| author_sort | Junfeng Xu |
| collection | DOAJ |
| description | Background: Colony-stimulating factor 3 (CSF3) is a cytokine that promotes inflammation by stimulating the maturation, proliferation, and trafficking of myeloid progenitor cells. However, the functional importance of CSF3 in colorectal cancer (CRC) remains unclear. Methods: CSF3 expression levels in CRC cells and tissues were detected by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC). In vitro and in vivo assays were performed to investigate the oncogenic function of CSF3 in the tumor associated malignant phenotypes and the tumorigenic capability of CRC cells. Immunocoprecipitation was performed to verify the regulatory effects of CSF3 on IκBα ubiquitination. Results: We found that CSF3 was overexpressed in CRC tissues compared to adjacent normal tissues, which correlated with poor patient survival. In vitro, silencing CSF3 significantly impaired cell proliferation, colony formation, and migration, while enhancing apoptosis. In vivo, silencing CSF3 resulted in reduced tumor growth, weight, and volume, indicating its potential as a therapeutic target. Mechanistically, CSF3 was found to mediate CRC development by activating the NF-κB signaling pathway, as evidenced by the decreased phosphorylation of p65 and reduced IκBα ubiquitination in CSF3-silenced cells. Furthermore, CSF3 silencing modulated immune infiltration in CRC, promoting an anti-tumor immune response and altering the tumor microenvironment. Conclusion: CSF3 modulated the NF-κB signaling pathway through a distinct mechanism involving p65 phosphorylation and the activation of NF-κB by enhancing IκBα ubiquitination, thereby effectively promoting CRC development, and CSF3 may serve as a potential therapeutic target for repressing CRC advance and metastasis. |
| format | Article |
| id | doaj-art-fbf321310c4d4284b47c41661895f8b9 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-fbf321310c4d4284b47c41661895f8b92025-02-10T04:34:18ZengElsevierTranslational Oncology1936-52332025-03-0153102310CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironmentJunfeng Xu0Na Li1Hui Xie2Changwei Duan3Xingchen Liao4Ruoran Li5Heng Zhang6Yuanming Pan7Xianzong Ma8Shuwen Du9Jianqiu Sheng10Xin Wang11Lang Yang12Peng Jin13Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, PR ChinaSenior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, PR China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR ChinaDepartment of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR ChinaMedical School of Chinese PLA, Beijing 100853, PR ChinaMedical School of Chinese PLA, Beijing 100853, PR ChinaMedical School of Chinese PLA, Beijing 100853, PR ChinaMedical School of Chinese PLA, Beijing 100853, PR ChinaCancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing 101149, PR ChinaSenior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, PR China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR ChinaDepartment of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR ChinaDepartment of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR ChinaDepartment of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR China; Corresponding authors.Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, PR China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR China; Corresponding authors.Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, PR China; Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, PR China; Corresponding authors.Background: Colony-stimulating factor 3 (CSF3) is a cytokine that promotes inflammation by stimulating the maturation, proliferation, and trafficking of myeloid progenitor cells. However, the functional importance of CSF3 in colorectal cancer (CRC) remains unclear. Methods: CSF3 expression levels in CRC cells and tissues were detected by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC). In vitro and in vivo assays were performed to investigate the oncogenic function of CSF3 in the tumor associated malignant phenotypes and the tumorigenic capability of CRC cells. Immunocoprecipitation was performed to verify the regulatory effects of CSF3 on IκBα ubiquitination. Results: We found that CSF3 was overexpressed in CRC tissues compared to adjacent normal tissues, which correlated with poor patient survival. In vitro, silencing CSF3 significantly impaired cell proliferation, colony formation, and migration, while enhancing apoptosis. In vivo, silencing CSF3 resulted in reduced tumor growth, weight, and volume, indicating its potential as a therapeutic target. Mechanistically, CSF3 was found to mediate CRC development by activating the NF-κB signaling pathway, as evidenced by the decreased phosphorylation of p65 and reduced IκBα ubiquitination in CSF3-silenced cells. Furthermore, CSF3 silencing modulated immune infiltration in CRC, promoting an anti-tumor immune response and altering the tumor microenvironment. Conclusion: CSF3 modulated the NF-κB signaling pathway through a distinct mechanism involving p65 phosphorylation and the activation of NF-κB by enhancing IκBα ubiquitination, thereby effectively promoting CRC development, and CSF3 may serve as a potential therapeutic target for repressing CRC advance and metastasis.http://www.sciencedirect.com/science/article/pii/S1936523325000415CSF3Colorectal cancerUbiquitinationp65/NF-κB signalingTumor microenvironment |
| spellingShingle | Junfeng Xu Na Li Hui Xie Changwei Duan Xingchen Liao Ruoran Li Heng Zhang Yuanming Pan Xianzong Ma Shuwen Du Jianqiu Sheng Xin Wang Lang Yang Peng Jin CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment Translational Oncology CSF3 Colorectal cancer Ubiquitination p65/NF-κB signaling Tumor microenvironment |
| title | CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment |
| title_full | CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment |
| title_fullStr | CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment |
| title_full_unstemmed | CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment |
| title_short | CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment |
| title_sort | csf3 promotes colorectal cancer progression by activating p65 nf κb signaling pathway and inducing an immunosuppressive microenvironment |
| topic | CSF3 Colorectal cancer Ubiquitination p65/NF-κB signaling Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000415 |
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