PRDX3 promotes nasopharyngeal carcinoma tumor growth by regulating PINK1/Parkin pathway-dependent lipid peroxidation and mitochondrial dysfunction

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-09-01 DOI:10.1016/j.yexcr.2025.114731

Hualong Qiang , Wei Wang , Xiaodong Zhan , Shiyin Ma

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引用次数: 0

Abstract

Background

Nasopharyngeal carcinoma (NPC) is a challenging malignancy characterized by aggressive progression and limited therapeutic efficacy. Emerging evidence implicates peroxiredoxin 3 (PRDX3), a mitochondrial peroxidase, as a critical regulator of redox homeostasis and mitochondrial integrity. Given its role in modulating cell death through mitochondrial quality control, we investigated the therapeutic potential of targeting PRDX3 in NPC.

Methods

PRDX3 expression patterns were assessed in clinical NPC specimens using immunohistochemical and immunoblotting. Functional studies employed siRNA-mediated PRDX3 knockdown followed by cellular assays: CCK-8 proliferation, clonogenic survival, and mitochondrial parameter quantification (reactive oxygen species flux using DCFH-DA/C11-BODIPY, ATP biosynthesis, membrane polarization, and mtDNA integrity). Molecular interplay between PRDX3 and PTEN-induced kinase 1 (PINK1) was elucidated through co-immunoprecipitation and immunofluorescence analysis. In vivo therapeutic efficacy was validated using a xenograft model to evaluate tumor growth modulation.

Results

Clinical specimens revealed significant PRDX3 overexpression in NPC compared to non-malignant controls. PRDX3 knockdown substantially attenuated malignant behavior and induced mitochondrial dysfunction in NPC cells. Mechanistically, PRDX3 interacted with PINK1 to stabilize Parkin-mediated mitophagic flux. PRDX3 safeguarded against apoptosis by sustaining PINK1/Parkin-dependent mitophagy clearance of damaged mitochondria. In vivo validation confirmed that PRDX3 knockdown suppressed tumor growth.

Conclusion

PRDX3 acts as an upstream activator of the PINK1/Parkin signaling cascade, regulating lipid peroxidation-mediated mitochondrial dysfunction, mitophagy, survival and apoptosis of NPC cell.

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PRDX3通过调节PINK1/Parkin通路依赖的脂质过氧化和线粒体功能障碍促进鼻咽癌肿瘤生长。

背景：鼻咽癌（NPC）是一种具有挑战性的恶性肿瘤，其特点是进展迅速，治疗效果有限。新出现的证据表明，过氧化物酶3 (PRDX3)，线粒体过氧化物酶，作为氧化还原稳态和线粒体完整性的关键调节器。鉴于其通过线粒体质量控制调节细胞死亡的作用，我们研究了靶向PRDX3在鼻咽癌中的治疗潜力。方法：应用免疫组化和免疫印迹法检测临床鼻咽癌标本中PRDX3的表达谱。功能研究采用sirna介导的PRDX3敲除，随后进行细胞分析：CCK-8增殖、克隆存活和线粒体参数量化（使用DCFH-DA/C11-BODIPY进行的活性氧通量、ATP生物合成、膜极化和mtDNA完整性）。通过共免疫沉淀和免疫荧光分析阐明了PRDX3与pten诱导的激酶1 （PINK1）之间的分子相互作用。利用异种移植模型评估肿瘤生长调节，验证了体内治疗效果。结果：与非恶性对照相比，临床标本显示PRDX3在鼻咽癌中明显过表达。PRDX3基因敲除可显著减弱鼻咽癌细胞的恶性行为并诱导线粒体功能障碍。在机制上，PRDX3与PINK1相互作用以稳定帕金森介导的有丝分裂通量。PRDX3通过维持受损线粒体的PINK1/ parkin依赖的线粒体自噬清除来保护细胞凋亡。体内验证证实PRDX3敲低抑制肿瘤生长。结论：PRDX3作为PINK1/Parkin信号级联的上游激活因子，调节脂质过氧化介导的鼻咽癌细胞线粒体功能障碍、线粒体自噬、存活和凋亡。

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

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.