Knockdown of TFB2M induces ferroptosis in lung adenocarcinoma via mitophagy-mediated GPX4 degradation.

IF 2.8 3区医学 Q2 ONCOLOGY

Expert Review of Anticancer Therapy Pub Date : 2025-09-03 DOI:10.1080/14737140.2025.2554642

Tulei Tian, Tianyu She, Meiling Xie, Xiangkun Qu, Hongbo Zhang, Gengyun Sun

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引用次数: 0

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, with a low survival rate. TFB2M, a mitochondrial transcription factor, maintains normal mitochondrial function. Its role in LUAD is unclear.

Methods: We analyzed TFB2M expression in LUAD and normal tissues based on TCGA database. GSEA analyzed pathway enrichment. TFB2M-knockdown LUAD and control groups were constructed. Western blot detected levels of mitophagy- and ferroptosis-related proteins with/without mitophagy inhibitor (Mdivi-1, 10 μM). Malondialdehyde, glutathione, 4-hydroxynonenal, reactive oxygen species, and Fe²⁺ levels were measured to evaluate ferroptosis. CCK-8, EdU experiments, and flow cytometry evaluated cell survival. Immunofluorescence detected co-localization of glutathione peroxidase 4 and mitochondrial outer membrane transferase 20. Mitochondrial-specific fluorescent probes evaluated mitochondrial changes. A LUAD xenograft mouse model was constructed, with tumor volume and weight (with/without mitophagy inhibitors, 50 mg/kg) measured. IHC detected TFB2M and ki67 expression.

Results: TFB2M was upregulated (p < 0.05), and enriched in ferroptosis and mitophagy-related pathways. Mitophagy inhibitors reversed the promotion of mitophagy and ferroptosis and the inhibition of cell proliferation conferred by TFB2M knockdown. In animal experiments, they weakened the inhibition of mitophagy and the alleviation of LUAD progression induced by TFB2M knockdown.

Conclusion: TFB2M contributes to ferroptosis resistance in LUAD by suppressing mitophagy.

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TFB2M的下调通过有丝自噬介导的GPX4降解诱导肺腺癌铁下垂。

背景：肺腺癌（LUAD）是最常见的肺癌亚型，生存率低。TFB2M是一种线粒体转录因子，维持正常的线粒体功能。它在LUAD中的作用尚不清楚。方法：基于TCGA数据库分析LUAD和正常组织中TFB2M的表达。GSEA分析途径富集。构建tfb2m敲低LUAD组和对照组。Western blot检测含/不含mitophagy inhibitor （mdivi - 1,10 μM）的小鼠线粒体自噬蛋白和凋亡相关蛋白水平。测定丙二醛、谷胱甘肽、4-羟基壬烯醛、活性氧和Fe2+水平以评估铁下垂。CCK-8、EdU实验和流式细胞术评估细胞存活率。免疫荧光检测谷胱甘肽过氧化物酶4和线粒体外膜转移酶20共定位。线粒体特异性荧光探针评估线粒体变化。建立LUAD异种移植小鼠模型，测量肿瘤体积和重量（含/不含线粒体自噬抑制剂，50 mg/kg）。IHC检测TFB2M和ki67的表达。结果：TFB2M上调(p)结论：TFB2M通过抑制线粒体自噬参与LUAD铁下垂抵抗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Anticancer Therapy 医学-肿瘤学

CiteScore

5.10

自引率

3.00%

发文量

100

审稿时长

4-8 weeks

期刊介绍： Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.