NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway
Abstract Background Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), ex...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-021-02138-w |
| _version_ | 1818586802009669632 |
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| author | Yun Wu Ying Lin Junfan Pan Xunwei Tu Yiquan Xu Hongru Li Yusheng Chen |
| author_facet | Yun Wu Ying Lin Junfan Pan Xunwei Tu Yiquan Xu Hongru Li Yusheng Chen |
| author_sort | Yun Wu |
| collection | DOAJ |
| description | Abstract Background Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers. Methods We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein–protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD. Results Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor β (TGF-β) signaling pathway. Additionally, rescue experiments indicated that TGF-β signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells. Conclusions NCAPG may promote proliferation and migration via the TGF-β signaling pathway in LUAD. |
| first_indexed | 2024-12-16T08:58:45Z |
| format | Article |
| id | doaj.art-a559c89a778f47168cdf27973f9249b3 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-16T08:58:45Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-a559c89a778f47168cdf27973f9249b32022-12-21T22:37:13ZengBMCCancer Cell International1475-28672021-08-0121111610.1186/s12935-021-02138-wNCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathwayYun Wu0Ying Lin1Junfan Pan2Xunwei Tu3Yiquan Xu4Hongru Li5Yusheng Chen6Shengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityAbstract Background Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers. Methods We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein–protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD. Results Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor β (TGF-β) signaling pathway. Additionally, rescue experiments indicated that TGF-β signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells. Conclusions NCAPG may promote proliferation and migration via the TGF-β signaling pathway in LUAD.https://doi.org/10.1186/s12935-021-02138-wLung adenocarcinomaNCAPGTGF-β signaling pathwayPrognostic biomarkers |
| spellingShingle | Yun Wu Ying Lin Junfan Pan Xunwei Tu Yiquan Xu Hongru Li Yusheng Chen NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway Cancer Cell International Lung adenocarcinoma NCAPG TGF-β signaling pathway Prognostic biomarkers |
| title | NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway |
| title_full | NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway |
| title_fullStr | NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway |
| title_full_unstemmed | NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway |
| title_short | NCAPG promotes the progression of lung adenocarcinoma via the TGF-β signaling pathway |
| title_sort | ncapg promotes the progression of lung adenocarcinoma via the tgf β signaling pathway |
| topic | Lung adenocarcinoma NCAPG TGF-β signaling pathway Prognostic biomarkers |
| url | https://doi.org/10.1186/s12935-021-02138-w |
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