PRDX6通过线粒体生物合成和氧化磷酸化驱动乳腺癌进展

IF 3.1 2区 医学 Q2 ONCOLOGY
Cancer Medicine Pub Date : 2025-06-30 DOI:10.1002/cam4.71005
Mei Dai, Danhua Zhang
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引用次数: 0

摘要

过氧化氧还蛋白6 (PRDX6)清除活性氧(ROS),在抗氧化防御中起关键作用。尽管PRDX6参与多种癌症,但其在乳腺癌(BRCA)中的作用尚不清楚。方法采用CCK-8、EdU染色、菌落形成法检测细胞增殖。通过伤口愈合和transwell试验评估迁移和侵袭。荧光显微镜或流式细胞术检测ROS水平和线粒体膜电位。氧化磷酸化(OXPHOS)活性通过ATP生成和NAD+/NADH比值测定。透射电镜观察线粒体,实时荧光定量PCR和Western blotting检测线粒体复合物亚基。使用异种移植肿瘤模型评估体内效应。结果PRDX6在BRCA中整体表达下调,但在侵袭性亚型和晚期肿瘤中表达升高,与预后不良相关。PRDX6的过表达增强了BRCA细胞的增殖、迁移和侵袭。PRDX6降低ROS水平,上调线粒体转录因子A (TFAM)表达,促进线粒体复合物亚基表达和OXPHOS。抑制TFAM导致一些线粒体复合物亚基的表达减少,从而逆转肿瘤的前致癌表型。PRDX6在体内也能促进肿瘤生长。结论PRDX6通过减少ROS维持细胞内稳态,并通过tfam依赖性和非依赖性途径促进线粒体生物发生和OXPHOS,推动BRCA的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PRDX6 Drives Breast Cancer Progression Through Mitochondrial Biosynthesis and Oxidative Phosphorylation

PRDX6 Drives Breast Cancer Progression Through Mitochondrial Biosynthesis and Oxidative Phosphorylation

Background

Peroxiredoxin 6 (PRDX6) scavenges reactive oxygen species (ROS) and plays a key role in antioxidant defense. Although PRDX6 is involved in various cancers, its role in breast cancer (BRCA) remains unclear.

Methods

Cell proliferation was assessed using CCK-8, EdU staining, and colony formation assays. Migration and invasion were evaluated via wound-healing and transwell assays. ROS levels and mitochondrial membrane potential were measured by fluorescence microscopy or flow cytometry. Oxidative phosphorylation (OXPHOS) activity was determined by ATP production and NAD+/NADH ratio. Mitochondria were visualized by TEM, and mitochondrial complex subunits were detected by quantitative real-time PCR and Western blotting. In vivo effects were evaluated using a xenograft tumor model.

Results

Although PRDX6 was downregulated in BRCA overall, it showed elevated expression in aggressive subtypes and advanced-stage tumors, correlating with poor prognosis. Overexpression of PRDX6 enhanced BRCA cell proliferation, migration, and invasion. PRDX6 reduced ROS levels, upregulated mitochondrial transcription factor A (TFAM) expression, and promoted mitochondrial complex subunit expression and OXPHOS. Inhibition of TFAM led to a decrease in the expression of some of the mitochondrial complex subunits, which reversed the pro-carcinogenic phenotype of the tumor. PRDX6 also promoted tumor growth in vivo.

Conclusion

PRDX6 maintains intracellular homeostasis by reducing ROS and promotes mitochondrial biogenesis and OXPHOS through TFAM-dependent and -independent pathways, driving BRCA progression.

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来源期刊
Cancer Medicine
Cancer Medicine ONCOLOGY-
CiteScore
5.50
自引率
2.50%
发文量
907
审稿时长
19 weeks
期刊介绍: Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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