Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma
Abstract Background Coix seed extract (CSE), a traditional Chinese medicine, has been reported as an adjunctive therapy in cancers. However, the molecular targets are largely unclear. The study is designed to unveil its function in lung adenocarcinoma (LUAD) and the possible molecular mechanism. Met...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cell Division |
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| Online Access: | https://doi.org/10.1186/s13008-024-00112-2 |
| _version_ | 1797273900733693952 |
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| author | Jiuyang Jiang Xue Li Chun Zhang Jiafu Wang Jin Li |
| author_facet | Jiuyang Jiang Xue Li Chun Zhang Jiafu Wang Jin Li |
| author_sort | Jiuyang Jiang |
| collection | DOAJ |
| description | Abstract Background Coix seed extract (CSE), a traditional Chinese medicine, has been reported as an adjunctive therapy in cancers. However, the molecular targets are largely unclear. The study is designed to unveil its function in lung adenocarcinoma (LUAD) and the possible molecular mechanism. Methods The HERB database was utilized to predict the molecular targets of the Coix seed, followed by prognostic value prediction in the Kaplan–Meier Plotter database. LUAD cells were infected with sh-KCTD9 after co-culture with CSE, and cell viability, growth, proliferation, and apoptosis were determined. The substrates of KCTD9 were predicted using a protein–protein interaction network and verified. The expression of PD-L1, the contents of TNF-α, IFN-γ, CXCL10, and CXCL9 in the co-culture system of LUAD cells and T cells and the proliferation of T cells were evaluated to study the immune escape of LUAD cells in response to CSE and sh-KCTD9. Lastly, tumor growth and immune escape were observed in tumor-bearing mice. Results CSE inhibited malignant behavior and immune escape of LUAD cells, and the reduction of KCTD9 reversed the inhibitory effect of CSE on malignant behavior and immune escape of LUAD cells. Knockdown of KCTD9 expression inhibited ubiquitination modification of TOP2A, and knockdown of TOP2A suppressed immune escape of LUAD cells in the presence of knockdown of KCTD9. CSE exerted anticancer effects in mice, but the reduction of KCTD9 partially compromised the anticancer effect of CSE. Conclusion CSE inhibits immune escape and malignant progression of LUAD through KCTD9-mediated ubiquitination modification of TOP2A. |
| first_indexed | 2024-03-07T14:50:45Z |
| format | Article |
| id | doaj.art-a4e60f3ae6374e2ea6c5fa6790ccf38a |
| institution | Directory Open Access Journal |
| issn | 1747-1028 |
| language | English |
| last_indexed | 2024-03-07T14:50:45Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj.art-a4e60f3ae6374e2ea6c5fa6790ccf38a2024-03-05T19:44:48ZengBMCCell Division1747-10282024-02-0119111510.1186/s13008-024-00112-2Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinomaJiuyang Jiang0Xue Li1Chun Zhang2Jiafu Wang3Jin Li4Department of Thoracic Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Internal Medicine, Daoli District People’s HospitalDepartment of Traditional Chinese Medicine, The First Affiliated Hospital of Harbin Medical UniversityDepartment of PET-CT, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Traditional Chinese Medicine, The Fourth Affiliated Hospital of Harbin Medical University SongbeiAbstract Background Coix seed extract (CSE), a traditional Chinese medicine, has been reported as an adjunctive therapy in cancers. However, the molecular targets are largely unclear. The study is designed to unveil its function in lung adenocarcinoma (LUAD) and the possible molecular mechanism. Methods The HERB database was utilized to predict the molecular targets of the Coix seed, followed by prognostic value prediction in the Kaplan–Meier Plotter database. LUAD cells were infected with sh-KCTD9 after co-culture with CSE, and cell viability, growth, proliferation, and apoptosis were determined. The substrates of KCTD9 were predicted using a protein–protein interaction network and verified. The expression of PD-L1, the contents of TNF-α, IFN-γ, CXCL10, and CXCL9 in the co-culture system of LUAD cells and T cells and the proliferation of T cells were evaluated to study the immune escape of LUAD cells in response to CSE and sh-KCTD9. Lastly, tumor growth and immune escape were observed in tumor-bearing mice. Results CSE inhibited malignant behavior and immune escape of LUAD cells, and the reduction of KCTD9 reversed the inhibitory effect of CSE on malignant behavior and immune escape of LUAD cells. Knockdown of KCTD9 expression inhibited ubiquitination modification of TOP2A, and knockdown of TOP2A suppressed immune escape of LUAD cells in the presence of knockdown of KCTD9. CSE exerted anticancer effects in mice, but the reduction of KCTD9 partially compromised the anticancer effect of CSE. Conclusion CSE inhibits immune escape and malignant progression of LUAD through KCTD9-mediated ubiquitination modification of TOP2A.https://doi.org/10.1186/s13008-024-00112-2Lung adenocarcinomaCoix seed extractKCTD9TOP2AUbiquitination modification |
| spellingShingle | Jiuyang Jiang Xue Li Chun Zhang Jiafu Wang Jin Li Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma Cell Division Lung adenocarcinoma Coix seed extract KCTD9 TOP2A Ubiquitination modification |
| title | Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma |
| title_full | Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma |
| title_fullStr | Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma |
| title_full_unstemmed | Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma |
| title_short | Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma |
| title_sort | anti cancer effects of coix seed extract through kctd9 mediated ubiquitination of top2a in lung adenocarcinoma |
| topic | Lung adenocarcinoma Coix seed extract KCTD9 TOP2A Ubiquitination modification |
| url | https://doi.org/10.1186/s13008-024-00112-2 |
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