Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis
Abstract Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechan...
| Autores principales: | , , , , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2024-01-01
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| Colección: | Cell Death and Disease |
| Acceso en línea: | https://doi.org/10.1038/s41419-024-06484-1 |
| _version_ | 1827326019528294400 |
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| author | Yunshang Chen Yun Zhou Xue Feng Zilong Wu Yongqiang Yang Xinrui Rao Rui Zhou Rui Meng Xiaorong Dong Shuangbing Xu Sheng Zhang Gang Wu Xiaohua Jie |
| author_facet | Yunshang Chen Yun Zhou Xue Feng Zilong Wu Yongqiang Yang Xinrui Rao Rui Zhou Rui Meng Xiaorong Dong Shuangbing Xu Sheng Zhang Gang Wu Xiaohua Jie |
| author_sort | Yunshang Chen |
| collection | DOAJ |
| description | Abstract Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechanistically, FBXO22 promoted Rad51 gene transcription by increasing the level of FOXM1 at the Rad51 promoter, thereby inducing the formation of lung cancer radioresistance. Furthermore, we found that deguelin, a potential inhibitor of FBXO22, enhanced radiosensitivity in an FBXO22/Rad51-dependent manner and was safely tolerated in vivo. Collectively, our results illustrate that FBXO22 induces lung cancer radioresistance by activating the FOXM1/Rad51 axis and provide preclinical evidence for the clinical translation of this critical target. |
| first_indexed | 2024-03-07T14:38:34Z |
| format | Article |
| id | doaj.art-24cc7d0f86ba4eb685bae0bb02f901b9 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-07T14:38:34Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-24cc7d0f86ba4eb685bae0bb02f901b92024-03-05T20:30:36ZengNature Publishing GroupCell Death and Disease2041-48892024-01-0115111310.1038/s41419-024-06484-1Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axisYunshang Chen0Yun Zhou1Xue Feng2Zilong Wu3Yongqiang Yang4Xinrui Rao5Rui Zhou6Rui Meng7Xiaorong Dong8Shuangbing Xu9Sheng Zhang10Gang Wu11Xiaohua Jie12Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechanistically, FBXO22 promoted Rad51 gene transcription by increasing the level of FOXM1 at the Rad51 promoter, thereby inducing the formation of lung cancer radioresistance. Furthermore, we found that deguelin, a potential inhibitor of FBXO22, enhanced radiosensitivity in an FBXO22/Rad51-dependent manner and was safely tolerated in vivo. Collectively, our results illustrate that FBXO22 induces lung cancer radioresistance by activating the FOXM1/Rad51 axis and provide preclinical evidence for the clinical translation of this critical target.https://doi.org/10.1038/s41419-024-06484-1 |
| spellingShingle | Yunshang Chen Yun Zhou Xue Feng Zilong Wu Yongqiang Yang Xinrui Rao Rui Zhou Rui Meng Xiaorong Dong Shuangbing Xu Sheng Zhang Gang Wu Xiaohua Jie Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis Cell Death and Disease |
| title | Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis |
| title_full | Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis |
| title_fullStr | Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis |
| title_full_unstemmed | Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis |
| title_short | Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis |
| title_sort | targeting fbxo22 enhances radiosensitivity in non small cell lung cancer by inhibiting the foxm1 rad51 axis |
| url | https://doi.org/10.1038/s41419-024-06484-1 |
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