Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner
Abstract Background CXC chemokine ligand 3 (CXCL3) is a member of CXC-type chemokine family that is identified as a major regulator in immune and inflammation responses. Recently, numerous evidence indicated that CXCL3 is broadly expressed in various human tumor types, and it is also known to play a...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11655-y |
| _version_ | 1797414846792204288 |
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| author | Yao Cheng Xinyan Yang Lichun Liang Hua Xin Xinyu Dong Weidong Li Jie Li Xiaoli Guo Yue Li Jian He Chunbin Zhang Weiqun Wang |
| author_facet | Yao Cheng Xinyan Yang Lichun Liang Hua Xin Xinyu Dong Weidong Li Jie Li Xiaoli Guo Yue Li Jian He Chunbin Zhang Weiqun Wang |
| author_sort | Yao Cheng |
| collection | DOAJ |
| description | Abstract Background CXC chemokine ligand 3 (CXCL3) is a member of CXC-type chemokine family that is identified as a major regulator in immune and inflammation responses. Recently, numerous evidence indicated that CXCL3 is broadly expressed in various human tumor types, and it is also known to play a critical role in mediating tumor development and progression. However, the expression profile of CXCL3 and the exact molecular mechanism behind the role of CXCL3 in colon adenocarcinoma (COAD) has not been fully elucidated. Methods The expression and clinical significance of CXCL3 mRNA and protein in the tissues from COAD patients were estimated using bioinformatics and immunohistochemistry assays. The expression and roles of exogenous administration or overexpression of CXCL3 in HT-29 and SW480 COAD cells were determined using enzyme-linked immunosorbent assay(ELISA), Cell Counting Kit-8 (CCK-8) and Transwell assays. Mechanically, CXCL3-induced malignant behaviors were elucidated using western blotting assay and extracellular signal-regulated protein kinase 1/2 (ERk1/2) inhibitor PD98059. Results The cancer genome atlas (TCGA)-COAD data analysis revealed that CXCL3 mRNA is highly expressed and has high clinical diagnostic accuracy in COAD. Increased expression of CXCL3 mRNA was associated with patient’s clinical stage, race, gender, age, histological subtype, nodal mestastasis and tumor protein 53 (TP53) mutation status. Similarly, immunohistochemistry assay also exhibited that CXCL3 protein in COAD tissues was significantly up-regulated. Gene expression associated assay implied that CXC chemokine ligand 1 (CXCL1) and CXC chemokine ligand 2 (CXCL2) were markedly correlated with CXCL3 in COAD. Protein-protein interaction (PPI) analysis revealed that cyclin B1 (CCNB1), mitotic arrest deficient 2 like 1 (MAD2L1), H2A family member Z (H2AFZ) and CXCL2 may be the important protein molecules involved in CXCL3-related tumor biology. Gene set enrichment analysis (GSEA) analysis revealed that CXCL3 was mainly enriched in the cell cycle, DNA replication, NOD-like receptors, NOTCH and transforming growth factor-β (TGF-β) Signal pathways. In vitro, exogenous administration or overexpression of CXCL3 resulted in increased malignant behaviors of HT-29 and SW480 cells, and down-regulation of CXCL3 expression inhibited the malignant behaviors of these tumor cells. In addition, overexpression of CXCL3 affected the expression of genes related to extracellular signal regulated kinase (ERK) pathway, including ERK1/2, p-ERK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cyclin D1. Finally, CXCL3-induced malignant behaviors in HT-29 and SW480 cells were obviously attenuated following treatment with ERK inhibitor PD98059. Conclusion CXCL3 is upregulated in COAD and plays a crucial role in the control of malignant behaviors of tumor cells, which indicated its involvement in the pathogenesis of COAD. |
| first_indexed | 2024-03-09T05:39:48Z |
| format | Article |
| id | doaj.art-1ebd04a3b31d43dca3cf703b36ae15a3 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-09T05:39:48Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-1ebd04a3b31d43dca3cf703b36ae15a32023-12-03T12:25:51ZengBMCBMC Cancer1471-24072023-11-0123111210.1186/s12885-023-11655-yElevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent mannerYao Cheng0Xinyan Yang1Lichun Liang2Hua Xin3Xinyu Dong4Weidong Li5Jie Li6Xiaoli Guo7Yue Li8Jian He9Chunbin Zhang10Weiqun Wang11Basic Medical College, Jiamusi UniversityBasic Medical College, Jiamusi UniversityBasic Medical College, Jiamusi UniversityFirst Affiliated Hospital, Jiamusi UniversityBasic Medical College, Jiamusi UniversityBasic Medical College, Jiamusi UniversityBasic Medical College, Jiamusi UniversityBasic Medical College, Jiamusi UniversityBasic Medical College, Jiamusi UniversityDepartment of Medical Technology, Collaborative Innovation Center for Translation Medical Testing and Application Technology Zhangzhou, Zhang Zhou Health Vocational CollegeDepartment of Medical Technology, Collaborative Innovation Center for Translation Medical Testing and Application Technology Zhangzhou, Zhang Zhou Health Vocational CollegeBasic Medical College, Jiamusi UniversityAbstract Background CXC chemokine ligand 3 (CXCL3) is a member of CXC-type chemokine family that is identified as a major regulator in immune and inflammation responses. Recently, numerous evidence indicated that CXCL3 is broadly expressed in various human tumor types, and it is also known to play a critical role in mediating tumor development and progression. However, the expression profile of CXCL3 and the exact molecular mechanism behind the role of CXCL3 in colon adenocarcinoma (COAD) has not been fully elucidated. Methods The expression and clinical significance of CXCL3 mRNA and protein in the tissues from COAD patients were estimated using bioinformatics and immunohistochemistry assays. The expression and roles of exogenous administration or overexpression of CXCL3 in HT-29 and SW480 COAD cells were determined using enzyme-linked immunosorbent assay(ELISA), Cell Counting Kit-8 (CCK-8) and Transwell assays. Mechanically, CXCL3-induced malignant behaviors were elucidated using western blotting assay and extracellular signal-regulated protein kinase 1/2 (ERk1/2) inhibitor PD98059. Results The cancer genome atlas (TCGA)-COAD data analysis revealed that CXCL3 mRNA is highly expressed and has high clinical diagnostic accuracy in COAD. Increased expression of CXCL3 mRNA was associated with patient’s clinical stage, race, gender, age, histological subtype, nodal mestastasis and tumor protein 53 (TP53) mutation status. Similarly, immunohistochemistry assay also exhibited that CXCL3 protein in COAD tissues was significantly up-regulated. Gene expression associated assay implied that CXC chemokine ligand 1 (CXCL1) and CXC chemokine ligand 2 (CXCL2) were markedly correlated with CXCL3 in COAD. Protein-protein interaction (PPI) analysis revealed that cyclin B1 (CCNB1), mitotic arrest deficient 2 like 1 (MAD2L1), H2A family member Z (H2AFZ) and CXCL2 may be the important protein molecules involved in CXCL3-related tumor biology. Gene set enrichment analysis (GSEA) analysis revealed that CXCL3 was mainly enriched in the cell cycle, DNA replication, NOD-like receptors, NOTCH and transforming growth factor-β (TGF-β) Signal pathways. In vitro, exogenous administration or overexpression of CXCL3 resulted in increased malignant behaviors of HT-29 and SW480 cells, and down-regulation of CXCL3 expression inhibited the malignant behaviors of these tumor cells. In addition, overexpression of CXCL3 affected the expression of genes related to extracellular signal regulated kinase (ERK) pathway, including ERK1/2, p-ERK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cyclin D1. Finally, CXCL3-induced malignant behaviors in HT-29 and SW480 cells were obviously attenuated following treatment with ERK inhibitor PD98059. Conclusion CXCL3 is upregulated in COAD and plays a crucial role in the control of malignant behaviors of tumor cells, which indicated its involvement in the pathogenesis of COAD.https://doi.org/10.1186/s12885-023-11655-ycolon CancerCXCL3MAPK/ERKMalignant behavior |
| spellingShingle | Yao Cheng Xinyan Yang Lichun Liang Hua Xin Xinyu Dong Weidong Li Jie Li Xiaoli Guo Yue Li Jian He Chunbin Zhang Weiqun Wang Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner BMC Cancer colon Cancer CXCL3 MAPK/ERK Malignant behavior |
| title | Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner |
| title_full | Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner |
| title_fullStr | Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner |
| title_full_unstemmed | Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner |
| title_short | Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner |
| title_sort | elevated expression of cxcl3 in colon cancer promotes malignant behaviors of tumor cells in an erk dependent manner |
| topic | colon Cancer CXCL3 MAPK/ERK Malignant behavior |
| url | https://doi.org/10.1186/s12885-023-11655-y |
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