Arecoline-induced EV-mediated ZNF582 hypermethylation drives IFIT1-PD-L1 immune evasion in oral squamous cell carcinoma.
Journal
Clinical epigenetics
Journal Volume
18
Journal Issue
1
Start Page
88
ISSN
1868-7083
Date Issued
2026-05-26
Author(s)
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.
Subjects
Arecoline
Extracellular vesicles (EVs)
IFIT1
Oral squamous cell carcinoma (OSCC)
PD-L
ZNF582
Type
journal article