TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis
Abstract Lung cancer is the most common cancer and the leading cause of cancer-related deaths. Developing therapies for lung cancer is challenging, and new targets are urgently required. TFIIB-related factor 2 (BRF2) plays a crucial role in the development and progression of various tumors. However,...
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| Format: | Article |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07813-8 |
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| author | Shen Yi Xing Qi Fei Luo Dingxin Wang Zitong Feng Luyuan Ma Wenhao Yu Cong Wang Hui Tian Ming Lu |
| author_facet | Shen Yi Xing Qi Fei Luo Dingxin Wang Zitong Feng Luyuan Ma Wenhao Yu Cong Wang Hui Tian Ming Lu |
| author_sort | Shen Yi |
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| description | Abstract Lung cancer is the most common cancer and the leading cause of cancer-related deaths. Developing therapies for lung cancer is challenging, and new targets are urgently required. TFIIB-related factor 2 (BRF2) plays a crucial role in the development and progression of various tumors. However, the potential role of BRF2 in lung squamous carcinoma (LUSC) is unclear. Therefore, the aim of this study was to elucidate the mechanism of BRF2 regulation in LUSC development. Flow cytometry, protein blotting, and in vivo experiments were performed to assess the function of BRF2 in LUSC. Transmission electron microscopy imaging and mitochondrial membrane potential (MMP) measurements were used to determine the effect of BRF2 on mitochondria in LUSC. The impact of the downstream molecule SLC8A3 was predicted using bioinformatics analysis, and the mechanism was investigated by analyzing quantitative reverse transcription-polymerase chain reaction and immunoprecipitation (IP) assays, which were confirmed through rescue experiments. BRF2 expression was upregulated in squamous carcinoma cells, which increased SLC8A3 protein expression, promoted mitochondrial autophagy, stabilized MMP, and reduced apoptosis. In addition, SLC8A3 overexpression inhibited PTEN-induced putative kinase 1 (PINK1) binding to TIMM23 to promote mitochondrial autophagy and stabilize the MMP, which counteracted BRF2 knockdown-induced apoptosis. BRF2 mediated SLC8A3 expression to reduce apoptosis in LUSC cells by maintaining mitochondrial homeostasis. These findings provide novel selective therapeutic targets and ideas for the treatment of LUSC. |
| format | Article |
| id | doaj-art-b89568f65e844de384c50ea559e5577d |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
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| series | Cell Death and Disease |
| spelling | doaj-art-b89568f65e844de384c50ea559e5577d2025-08-20T03:42:00ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111210.1038/s41419-025-07813-8TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasisShen Yi0Xing Qi1Fei Luo2Dingxin Wang3Zitong Feng4Luyuan Ma5Wenhao Yu6Cong Wang7Hui Tian8Ming Lu9Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversitySchool of Public Health, North China University of Science and TechnologyDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan HospitalDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract Lung cancer is the most common cancer and the leading cause of cancer-related deaths. Developing therapies for lung cancer is challenging, and new targets are urgently required. TFIIB-related factor 2 (BRF2) plays a crucial role in the development and progression of various tumors. However, the potential role of BRF2 in lung squamous carcinoma (LUSC) is unclear. Therefore, the aim of this study was to elucidate the mechanism of BRF2 regulation in LUSC development. Flow cytometry, protein blotting, and in vivo experiments were performed to assess the function of BRF2 in LUSC. Transmission electron microscopy imaging and mitochondrial membrane potential (MMP) measurements were used to determine the effect of BRF2 on mitochondria in LUSC. The impact of the downstream molecule SLC8A3 was predicted using bioinformatics analysis, and the mechanism was investigated by analyzing quantitative reverse transcription-polymerase chain reaction and immunoprecipitation (IP) assays, which were confirmed through rescue experiments. BRF2 expression was upregulated in squamous carcinoma cells, which increased SLC8A3 protein expression, promoted mitochondrial autophagy, stabilized MMP, and reduced apoptosis. In addition, SLC8A3 overexpression inhibited PTEN-induced putative kinase 1 (PINK1) binding to TIMM23 to promote mitochondrial autophagy and stabilize the MMP, which counteracted BRF2 knockdown-induced apoptosis. BRF2 mediated SLC8A3 expression to reduce apoptosis in LUSC cells by maintaining mitochondrial homeostasis. These findings provide novel selective therapeutic targets and ideas for the treatment of LUSC.https://doi.org/10.1038/s41419-025-07813-8 |
| spellingShingle | Shen Yi Xing Qi Fei Luo Dingxin Wang Zitong Feng Luyuan Ma Wenhao Yu Cong Wang Hui Tian Ming Lu TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis Cell Death and Disease |
| title | TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis |
| title_full | TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis |
| title_fullStr | TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis |
| title_full_unstemmed | TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis |
| title_short | TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial homeostasis |
| title_sort | tfiib related factor 2 inhibits lung squamous carcinoma cell apoptosis through slc8a3 mediated mitochondrial homeostasis |
| url | https://doi.org/10.1038/s41419-025-07813-8 |
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