FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context
Background: Chemoresistance is a major obstacle for the effective treatment of lung adenocarcinoma (LAD). Forkhead box (FOX) proteins have been demonstrated to play critical roles in promoting epithelial-mesenchymal transition (EMT) and chemoresistance. However, whether FOX proteins contribute to th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419303548 |
| _version_ | 1818302720915800064 |
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| author | Dongqin Chen Rui Wang Chen Yu Fei Cao Xuefeng Zhang Feng Yan Longbang Chen Hong Zhu Zhengyuan Yu Jifeng Feng |
| author_facet | Dongqin Chen Rui Wang Chen Yu Fei Cao Xuefeng Zhang Feng Yan Longbang Chen Hong Zhu Zhengyuan Yu Jifeng Feng |
| author_sort | Dongqin Chen |
| collection | DOAJ |
| description | Background: Chemoresistance is a major obstacle for the effective treatment of lung adenocarcinoma (LAD). Forkhead box (FOX) proteins have been demonstrated to play critical roles in promoting epithelial-mesenchymal transition (EMT) and chemoresistance. However, whether FOX proteins contribute to the acquisition of EMT and chemoresistance in LAD remains largely unknown. Methods: FOX-A1 expression was measured in LAD cells and tissues by qRT-PCR. The expression levels of EMT markers were detected by western blotting and immunofluorescence assay. The interaction between Sex determining region Y-box protein 5 (SOX5) and FOX-A1 was validated by chromatin immunoprecipitation sequence (ChIP-seq) and Chromatin immunoprecipitation (ChIP) assay. Kaplan-Meier analysis and multivariate Cox regression analysis were performed to analyze the significance of FOX-A1 and SOX5 expression in the prognosis of LAD patients. Findings: FOX-A1 was upregulated in docetaxel-resistant LAD cells. High FOX-A1 expression was closely associated with a worse prognosis. Upregulation of FOX-A1 in LAD samples indicated short progression-free survival (PFS) and overall survival (OS). SOX5 is a new and direct target of FOX-A1 and was positively regulated by FOX-A1 in LAD cell lines. Knockdown of FOX-A1 or SOX5 reversed the chemoresistance of docetaxel-resistant LAD cells by suppressing cell proliferation, migration and EMT progress. Interpretation: These data elucidated an original FOX-A1/SOX5 pathway that represents a promising therapeutic target for chemosensitizing LAD and provides predictive biomarkers for evaluating the efficacy of chemotherapies. Keywords: Lung adenocarcinoma, Chemoresistance, FOX-A1, SOX5 |
| first_indexed | 2024-12-13T05:43:24Z |
| format | Article |
| id | doaj.art-ced098d17e0a405daecae0642c687713 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T05:43:24Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-ced098d17e0a405daecae0642c6877132022-12-21T23:57:44ZengElsevierEBioMedicine2352-39642019-06-0144150161FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in contextDongqin Chen0Rui Wang1Chen Yu2Fei Cao3Xuefeng Zhang4Feng Yan5Longbang Chen6Hong Zhu7Zhengyuan Yu8Jifeng Feng9Department of Medical Oncology, Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China; Department of Medical Oncology, Nanjing General Hospital of Nanjing Military Command, School of Medicine, Nanjing University, Nanjing, ChinaDepartment of Medical Oncology, Nanjing General Hospital of Nanjing Military Command, School of Medicine, Nanjing University, Nanjing, ChinaDepartment of Medical Oncology, Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, ChinaWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem,USA; Department of Urology, the First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Medical Oncology, Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Medical Oncology, Nanjing General Hospital of Nanjing Military Command, School of Medicine, Nanjing University, Nanjing, ChinaDepartment of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China; Corresponding authors at: Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting Road, Nanjing 210009, Jiangsu, China; Department of Medical Oncology, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, China.Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China; Corresponding authors at: Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting Road, Nanjing 210009, Jiangsu, China; Department of Medical Oncology, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, China.Department of Medical Oncology, Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; Correspondence to: J. Feng, Department of Medical Oncology, Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting Road, Nanjing 210009, Jiangsu, China.Background: Chemoresistance is a major obstacle for the effective treatment of lung adenocarcinoma (LAD). Forkhead box (FOX) proteins have been demonstrated to play critical roles in promoting epithelial-mesenchymal transition (EMT) and chemoresistance. However, whether FOX proteins contribute to the acquisition of EMT and chemoresistance in LAD remains largely unknown. Methods: FOX-A1 expression was measured in LAD cells and tissues by qRT-PCR. The expression levels of EMT markers were detected by western blotting and immunofluorescence assay. The interaction between Sex determining region Y-box protein 5 (SOX5) and FOX-A1 was validated by chromatin immunoprecipitation sequence (ChIP-seq) and Chromatin immunoprecipitation (ChIP) assay. Kaplan-Meier analysis and multivariate Cox regression analysis were performed to analyze the significance of FOX-A1 and SOX5 expression in the prognosis of LAD patients. Findings: FOX-A1 was upregulated in docetaxel-resistant LAD cells. High FOX-A1 expression was closely associated with a worse prognosis. Upregulation of FOX-A1 in LAD samples indicated short progression-free survival (PFS) and overall survival (OS). SOX5 is a new and direct target of FOX-A1 and was positively regulated by FOX-A1 in LAD cell lines. Knockdown of FOX-A1 or SOX5 reversed the chemoresistance of docetaxel-resistant LAD cells by suppressing cell proliferation, migration and EMT progress. Interpretation: These data elucidated an original FOX-A1/SOX5 pathway that represents a promising therapeutic target for chemosensitizing LAD and provides predictive biomarkers for evaluating the efficacy of chemotherapies. Keywords: Lung adenocarcinoma, Chemoresistance, FOX-A1, SOX5http://www.sciencedirect.com/science/article/pii/S2352396419303548 |
| spellingShingle | Dongqin Chen Rui Wang Chen Yu Fei Cao Xuefeng Zhang Feng Yan Longbang Chen Hong Zhu Zhengyuan Yu Jifeng Feng FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context EBioMedicine |
| title | FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context |
| title_full | FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context |
| title_fullStr | FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context |
| title_full_unstemmed | FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context |
| title_short | FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5Research in context |
| title_sort | fox a1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of sox5research in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419303548 |
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