Arecoline-induced EV-mediated ZNF582 hypermethylation drives IFIT1-PD-L1 immune evasion in oral squamous cell carcinoma.

IF 4.4 2区医学 Q1 GENETICS & HEREDITY

Clinical Epigenetics Pub Date : 2026-05-26 DOI:10.1186/s13148-026-02066-4

Hui-Hsin Ko, Hsin-Hui Peng, Chun-Pin Chiang, Hsiang-Fong Kao, Hung-Ying Lin, Mark Yen-Ping Kuo, Shih-Jung Cheng

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引用次数: 0

Abstract

Background: This study examined the role of arecoline-induced zinc finger protein 582 (ZNF582) methylation via extracellular vesicles (EVs) in oral squamous cell carcinoma (OSCC) and its effect on PD-L1 expression through the interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) pathway.

Materials and methods: EVs were isolated from SAS and TW2.6 cancer cell lines using ultracentrifugation and characterized using electron microscopy. ZNF582 methylation and protein expression were assessed, with stemness and epithelial-mesenchymal transition (EMT) markers analyzed via Western blotting. T cell populations were evaluated using flow cytometry.

Results: Arecoline-induced ZNF582 methylation via EVs reduced protein expression. ZNF582 knockdown promoted OSCC proliferation, migration, stemness, and EMT, and increased PD-L1 expression, aiding immune evasion via IFIT1. PD-L1 expression was linked to lower CD4+/CD8 + T cell ratios in OSCC patients.

Conclusion: Arecoline-induced ZNF582 hypermethylation via EVs promotes immune evasion through IFIT1, suggesting a potential therapeutic target for OSCC treatment.

Clinical relevance: Targeting the EV-mediated ZNF582-IFIT1-PD-L1 pathway may offer new therapeutic strategies for immune modulation in OSCC patients, especially those with a history of areca nut exposure.

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槟榔碱诱导的ev介导的ZNF582高甲基化驱动口腔鳞状细胞癌中IFIT1-PD-L1免疫逃避。

背景：本研究通过细胞外囊泡（EVs）检测槟槟碱诱导锌指蛋白582 （ZNF582）甲基化在口腔鳞状细胞癌（OSCC）中的作用，并通过干扰素诱导蛋白与四肽重复1 （IFIT1）途径检测其对PD-L1表达的影响。材料与方法：采用超离心法从SAS和TW2.6癌细胞中分离出ev，并用电镜对其进行表征。评估ZNF582甲基化和蛋白表达，并通过Western blotting分析干细胞的干性和上皮-间质转化（EMT）标记。使用流式细胞术评估T细胞群。结果：槟榔碱通过ev诱导的ZNF582甲基化降低了蛋白表达。ZNF582敲低可促进OSCC增殖、迁移、干性和EMT，并增加PD-L1表达，通过IFIT1促进免疫逃避。在OSCC患者中，PD-L1表达与较低的CD4+/CD8 + T细胞比率有关。结论：槟榔碱通过ev诱导的ZNF582高甲基化可通过IFIT1促进免疫逃避，可能是OSCC治疗的潜在治疗靶点。临床意义：靶向ev介导的ZNF582-IFIT1-PD-L1通路可能为OSCC患者的免疫调节提供新的治疗策略，特别是那些有槟榔暴露史的患者。

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来源期刊

Clinical Epigenetics ONCOLOGY-

自引率

5.30%

发文量

150

期刊介绍： Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.