Wu Shang, Ma Xindi, Zhang Xiangmei, Du Kaiye, Shi Chao, Almaamari Ahmed Ali, Han Boye, Su Suwen, Liu Yunjiang
Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Hebei Medical University, Shijiazhuang, China.
Cancer Biol Ther. 2025 Dec;26(1):2445220. doi: 10.1080/15384047.2024.2445220. Epub 2024 Dec 20.
While NDUFAF6 is implicated in breast cancer, its specific role remains unclear.
The expression levels and prognostic significance of NDUFAF6 in breast cancer were assessed using The Cancer Genome Atlas, Gene Expression Omnibus, Kaplan-Meier plotter and cBio-Portal databases. We knocked down NDUFAF6 in breast cancer cells using small interfering RNA and investigated its effects on cell proliferation and migration ability. We performed gene expression analysis and validated key findings using protein analysis. We also assessed mitochondrial activity and cellular metabolism.
NDUFAF6 was highly expressed in breast cancer, which was associated with a poorer prognosis. Knockdown of NDUFAF6 reduced the proliferation and migration ability of breast cancer cells. Transcriptome analysis revealed 2,101 differentially expressed genes enriched in apoptosis and mitochondrial signaling pathways. Western blot results showed NDUFAF6 knockdown enhanced apoptosis. In addition, differential gene enrichment analysis was related to mitochondrial signaling pathways, and western blot results verified that mitophagy was enhanced in NDUFAF6 knockdown breast cancer cells. JC-1 assay also showed that mitochondrial dysfunction and reactive oxygen species content were increased after knocking down NDUFAF6. In addition, basal and maximal mitochondrial oxygen consumption decreased, and intracellular glycogen content increased.
Knockdown of NDUFAF6 resulted in apoptosis and mitophagy in breast cancer cells and NDUFAF6 may be a potential molecular target for breast cancer therapy.
虽然 NDUFAF6 与乳腺癌有关，但其具体作用仍不清楚。
使用癌症基因组图谱、基因表达综合数据库、Kaplan-Meier 绘图仪和 cBio-Portal 数据库评估 NDUFAF6 在乳腺癌中的表达水平和预后意义。我们使用小干扰 RNA 在乳腺癌细胞中敲低 NDUFAF6，并研究其对细胞增殖和迁移能力的影响。我们进行了基因表达分析，并使用蛋白质分析验证了关键发现。我们还评估了线粒体活性和细胞代谢。
NDUFAF6 在乳腺癌中高表达，这与较差的预后相关。敲低 NDUFAF6 降低了乳腺癌细胞的增殖和迁移能力。转录组分析揭示了 2101 个差异表达基因，这些基因富集于凋亡和线粒体信号通路。蛋白质印迹结果显示，敲低 NDUFAF6 增强了凋亡。此外，差异基因富集分析与线粒体信号通路有关，蛋白质印迹结果证实，敲低 NDUFAF6 的乳腺癌细胞中线粒体自噬增强。JC-1 检测还显示，敲低 NDUFAF6 后线粒体功能障碍和活性氧含量增加。此外，基础和最大线粒体耗氧量降低，细胞内糖原含量增加。
敲低 NDUFAF6 导致乳腺癌细胞凋亡和线粒体自噬，NDUFAF6 可能是乳腺癌治疗的潜在分子靶点。
