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TFIIB-related factor 2 inhibits lung squamous carcinoma cell apoptosis through SLC8A3-mediated mitochondrial
1Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
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.
Insights
TFIIB-related factor 2 (BRF2) upregulation in lung squamous cell carcinoma (LUSC) promotes tumor growth by increasing SLC8A3, stabilizing mitochondrial function, and reducing apoptosis. This reveals BRF2 as a potential therapeutic target for LUSC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Lung cancer is a leading cause of cancer deaths, necessitating novel therapeutic targets.
- TFIIB-related factor 2 (BRF2) is implicated in tumor development, but its role in lung squamous carcinoma (LUSC) remains undefined.
Purpose of the Study:
- To investigate the regulatory mechanism and functional role of BRF2 in LUSC development.
- To elucidate the downstream targets and signaling pathways affected by BRF2 in LUSC.
Main Methods:
- Flow cytometry, Western blotting, and in vivo experiments assessed BRF2 function.
- Transmission electron microscopy and mitochondrial membrane potential (MMP) assays evaluated mitochondrial effects.
- Bioinformatics, qRT-PCR, and immunoprecipitation (IP) assays identified and confirmed SLC8A3 as a downstream mediator.
Main Results:
- BRF2 was upregulated in LUSC, increasing SLC8A3 expression and promoting mitochondrial autophagy.
- BRF2 stabilized MMP and reduced apoptosis in LUSC cells.
- SLC8A3 overexpression counteracted BRF2 knockdown effects by inhibiting PINK1-TIMM23 interaction, further promoting mitochondrial autophagy.
Conclusions:
- BRF2 maintains mitochondrial homeostasis in LUSC by mediating SLC8A3 expression, thereby reducing apoptosis.
- BRF2 and its downstream effector SLC8A3 represent promising therapeutic targets for LUSC treatment.
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