EBV-Derived miR-BART20-3p Influences Proliferation and Migration in EBV-Positive Gastric Cancer Models by Suppressing PPARα

EBV-Derived miR-BART20-3p Influences Proliferation and Migration in EBV-Positive Gastric Cancer Models by Suppressing PPARα

Epstein–Barr virus (EBV) is the first oncogenic DNA virus known to encode microRNAs (miRNAs) and has been implicated in the pathogenesis of multiple malignancies, including a distinct subset of gastric cancers (EBV-associated gastric cancer, EBVaGC). However, the functional roles of individual EBV-e...

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Bibliographic Details
Main Authors: Qiong Wu, Guiying Ye, Xiazhen Xu, Xianchang Zeng, Biyun Wu, Fan Xin, Lu Zhang, Xu Lin, Xinjian Lin, Wannan Chen
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
Subjects:
Epstein–Barr virus-encoded miRNAs
miRNA-BART20-3p
gastric cancer
PPARα
IL-6
cell proliferation
Online Access:https://www.mdpi.com/2076-2607/13/7/1514
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Summary:Epstein–Barr virus (EBV) is the first oncogenic DNA virus known to encode microRNAs (miRNAs) and has been implicated in the pathogenesis of multiple malignancies, including a distinct subset of gastric cancers (EBV-associated gastric cancer, EBVaGC). However, the functional roles of individual EBV-encoded miRNAs in EBVaGC remain poorly defined. In this study, we integrate bioinformatic and experimental analyses to uncover a novel oncogenic axis driven by EBV-encoded miR-BART20-3p. Analysis of public transcriptomic datasets revealed that peroxisome proliferator-activated receptor α (PPARα) is significantly downregulated in EBVaGC compared with EBV-negative gastric tumors. We confirmed that both PPARα mRNA and protein are reduced in EBVaGC cell lines and primary tumor specimens, and that this reduction inversely correlates with miR-BART20-3p levels. A dual-luciferase reporter assay demonstrated that miR-BART20-3p directly binds the PPARα 3′-UTR. Functionally, miR-BART20-3p overexpression in AGS cells enhanced proliferation and migration, whereas inhibition of miR-BART20-3p in EBV-infected AGS cells attenuated these phenotypes. Mechanistic studies employing PPARα-specific siRNA together with qRT-PCR and ELISA reveal that suppression of PPARα or overexpression of miR-BART20-3p leads to upregulation of interleukin 6 (IL-6), indicating disruption of the PPARα–IL-6 regulatory axis. Collectively, EBV-encoded miR-BART20-3p promotes EBVaGC progression by directly targeting PPARα, and thereby derepressing IL-6 expression. This miRNA–PPARα–IL-6 pathway may serve as both a mechanistic biomarker and a novel therapeutic target in EBVaGC.
ISSN:2076-2607

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