CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway
Abstract Background The upregulated expression of CXCL1 has been validated in colorectal cancer patients. As a potential biotherapeutic target for colorectal cancer, the mechanism by which CXCL1 affects the development of colorectal cancer is not clear. Methods Expression data of CXCL1 in colorectal...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Biology Direct |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13062-022-00348-4 |
| _version_ | 1797986850400370688 |
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| author | Changhua Zhuo Qiang Ruan Xiangqian Zhao Yangkun Shen Ruirong Lin |
| author_facet | Changhua Zhuo Qiang Ruan Xiangqian Zhao Yangkun Shen Ruirong Lin |
| author_sort | Changhua Zhuo |
| collection | DOAJ |
| description | Abstract Background The upregulated expression of CXCL1 has been validated in colorectal cancer patients. As a potential biotherapeutic target for colorectal cancer, the mechanism by which CXCL1 affects the development of colorectal cancer is not clear. Methods Expression data of CXCL1 in colorectal cancer were obtained from the GEO database and verified using the GEPIA database and the TIMER 2.0 database. Knockout and overexpression of CXCL1 in colorectal cancer cells by CRISPR/Cas and "Sleeping Beauty" transposon-mediated gene editing techniques. Cell biological function was demonstrated by CCK-8, transwell chamber and Colony formation assay. RT-qPCR and Western Blot assays measured RNA and protein expression. Protein localization and expression were measured by immunohistochemistry and immunofluorescence. Results Bioinformatics analysis showed significant overexpression of CXCL1 in the colorectal cancer tissues compared to normal human tissues, and identified CXCL1 as a potential therapeutic target for colorectal cancer. We demonstrate that CXCL1 promotes the proliferation and migration of colon cancer cells and has a facilitative effect on tumor angiogenesis. Furthermore, CXCL1 elevation promoted the migration of M2-tumor associated macrophages (TAMs) while disrupting the aggregation of CD4+ and CD8+ T cells at tumor sites. Mechanistic studies suggested that CXCL1 activates the NF-κB pathway. In the in vivo colon cancer transplantation tumor model, treatment with the P300 inhibitor C646 significantly inhibited the growth of CXCL1-overexpressing colon cancer. Conclusion CXCL1 promotes colon cancer development through activation of NF-κB/P300, and that CXCL1-based therapy is a potential novel strategy to prevent colon cancer development. |
| first_indexed | 2024-04-11T07:39:24Z |
| format | Article |
| id | doaj.art-41a46262101c457a8811aea2085df033 |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-04-11T07:39:24Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-41a46262101c457a8811aea2085df0332022-12-22T04:36:38ZengBMCBiology Direct1745-61502022-11-0117111710.1186/s13062-022-00348-4CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathwayChanghua Zhuo0Qiang Ruan1Xiangqian Zhao2Yangkun Shen3Ruirong Lin4Department of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalFuzhou University, College of ChemistryFujian Normal University Qishan Campus, College of Life Science, Biomedical Research Center of South ChinaFujian Normal University Qishan Campus, College of Life Science, Biomedical Research Center of South ChinaDepartment of Gastrointestinal Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer HospitalAbstract Background The upregulated expression of CXCL1 has been validated in colorectal cancer patients. As a potential biotherapeutic target for colorectal cancer, the mechanism by which CXCL1 affects the development of colorectal cancer is not clear. Methods Expression data of CXCL1 in colorectal cancer were obtained from the GEO database and verified using the GEPIA database and the TIMER 2.0 database. Knockout and overexpression of CXCL1 in colorectal cancer cells by CRISPR/Cas and "Sleeping Beauty" transposon-mediated gene editing techniques. Cell biological function was demonstrated by CCK-8, transwell chamber and Colony formation assay. RT-qPCR and Western Blot assays measured RNA and protein expression. Protein localization and expression were measured by immunohistochemistry and immunofluorescence. Results Bioinformatics analysis showed significant overexpression of CXCL1 in the colorectal cancer tissues compared to normal human tissues, and identified CXCL1 as a potential therapeutic target for colorectal cancer. We demonstrate that CXCL1 promotes the proliferation and migration of colon cancer cells and has a facilitative effect on tumor angiogenesis. Furthermore, CXCL1 elevation promoted the migration of M2-tumor associated macrophages (TAMs) while disrupting the aggregation of CD4+ and CD8+ T cells at tumor sites. Mechanistic studies suggested that CXCL1 activates the NF-κB pathway. In the in vivo colon cancer transplantation tumor model, treatment with the P300 inhibitor C646 significantly inhibited the growth of CXCL1-overexpressing colon cancer. Conclusion CXCL1 promotes colon cancer development through activation of NF-κB/P300, and that CXCL1-based therapy is a potential novel strategy to prevent colon cancer development.https://doi.org/10.1186/s13062-022-00348-4CXCL1Colon cancerNF-κBP300C646 |
| spellingShingle | Changhua Zhuo Qiang Ruan Xiangqian Zhao Yangkun Shen Ruirong Lin CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway Biology Direct CXCL1 Colon cancer NF-κB P300 C646 |
| title | CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway |
| title_full | CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway |
| title_fullStr | CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway |
| title_full_unstemmed | CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway |
| title_short | CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway |
| title_sort | cxcl1 promotes colon cancer progression through activation of nf κb p300 signaling pathway |
| topic | CXCL1 Colon cancer NF-κB P300 C646 |
| url | https://doi.org/10.1186/s13062-022-00348-4 |
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