CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma
Objective: The E3 ligase, CRL4, plays diverse roles in different cellular processes, such as DNA damage, transcriptional regulation, cell cycle progression, and cell apoptosis. Our previous study showed that CUL4A and CUL4B had a strong association with tobacco smoking risk in lung squamous cell car...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2020-05-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1615 |
| _version_ | 1818879930222510080 |
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| author | Ting Li Si Wu Lei Jia Wenfeng Cao Yuan Yao Gang Zhao Hui Li |
| author_facet | Ting Li Si Wu Lei Jia Wenfeng Cao Yuan Yao Gang Zhao Hui Li |
| author_sort | Ting Li |
| collection | DOAJ |
| description | Objective: The E3 ligase, CRL4, plays diverse roles in different cellular processes, such as DNA damage, transcriptional regulation, cell cycle progression, and cell apoptosis. Our previous study showed that CUL4A and CUL4B had a strong association with tobacco smoking risk in lung squamous cell carcinoma (SCC) and small cell lung carcinoma (SCLC). This study aimed to define the potential mechanism underlying the roles of CUL4A and CUL4B in the development of SCC and SCLC. Methods: We determined the role of CUL4A and CUL4B in the cell cycle and apoptosis of SCC and SCLC, and identified the key apoptosis-related gene involved in the oncogenic activity of CUL4B by Western blot, immunohistochemical staining, flow cytometry, and enzyme inhibition experiments. Results: We found that depletion of CUL4A and CUL4B reduced the proliferation of SCC and SCLC cells. CUL4Aknockdown but not CUL4Bknockdown arrested cells in G1 phase while upregulating P21 and CUL4Bknockdown promoted cell apoptosis through upregulation of FOXO3A. Accordingly, CUL4B decreased FOXO3A expression by activating the ERK signaling pathway and mediating FOXO3A degradation via the ubiquitin-proteasome pathway. Conclusions: These results identified the function of E3 ligase CRL4 in regulating SCC and SCLC cell proliferation, which provides a potential strategy for cancer therapy by targeting FOXO3A and the E3 ligase, CRL4. |
| first_indexed | 2024-12-19T14:37:54Z |
| format | Article |
| id | doaj.art-98a5a54d3605449cb0e85b5b05b3ef83 |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-12-19T14:37:54Z |
| publishDate | 2020-05-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-98a5a54d3605449cb0e85b5b05b3ef832022-12-21T20:17:11ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412020-05-0117235737010.20892/j.issn.2095-3941.2019.0107CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinomaTing Li0Si Wu1Lei Jia2Wenfeng Cao3Yuan Yao4Gang Zhao5Hui Li6Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaKey Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaDepartment of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaObjective: The E3 ligase, CRL4, plays diverse roles in different cellular processes, such as DNA damage, transcriptional regulation, cell cycle progression, and cell apoptosis. Our previous study showed that CUL4A and CUL4B had a strong association with tobacco smoking risk in lung squamous cell carcinoma (SCC) and small cell lung carcinoma (SCLC). This study aimed to define the potential mechanism underlying the roles of CUL4A and CUL4B in the development of SCC and SCLC. Methods: We determined the role of CUL4A and CUL4B in the cell cycle and apoptosis of SCC and SCLC, and identified the key apoptosis-related gene involved in the oncogenic activity of CUL4B by Western blot, immunohistochemical staining, flow cytometry, and enzyme inhibition experiments. Results: We found that depletion of CUL4A and CUL4B reduced the proliferation of SCC and SCLC cells. CUL4Aknockdown but not CUL4Bknockdown arrested cells in G1 phase while upregulating P21 and CUL4Bknockdown promoted cell apoptosis through upregulation of FOXO3A. Accordingly, CUL4B decreased FOXO3A expression by activating the ERK signaling pathway and mediating FOXO3A degradation via the ubiquitin-proteasome pathway. Conclusions: These results identified the function of E3 ligase CRL4 in regulating SCC and SCLC cell proliferation, which provides a potential strategy for cancer therapy by targeting FOXO3A and the E3 ligase, CRL4.http://www.cancerbiomed.org/index.php/cocr/article/view/1615squamous cell lung cancersmall cell lung cancercul4acul4bp21foxo3a |
| spellingShingle | Ting Li Si Wu Lei Jia Wenfeng Cao Yuan Yao Gang Zhao Hui Li CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma Cancer Biology & Medicine squamous cell lung cancer small cell lung cancer cul4a cul4b p21 foxo3a |
| title | CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma |
| title_full | CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma |
| title_fullStr | CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma |
| title_full_unstemmed | CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma |
| title_short | CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma |
| title_sort | cul4 e3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma |
| topic | squamous cell lung cancer small cell lung cancer cul4a cul4b p21 foxo3a |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1615 |
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