ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2020
Epstein-Barr virus-encoded miR-BART5-5p upregulates PD-L1 through PIAS3/pSTAT3 modulation, worsening clinical outcomes of PD-L1-positive gastric carcinomas.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Epstein-Barr virus-driven immunosuppression in nasopharyngeal carcinoma: a comprehensive review of viral mechanisms, spatial tumor ecosystems, and precision therapeutics.Frontiers in immunology · 2026Pooled it
- Korean Practice Guidelines for Gastric Cancer 2024: An Evidence-based, Multidisciplinary Approach (Update of 2022 Guideline).Journal of gastric cancer · 2025Guideline
- Unlocking the potential of microRNA as predictive biomarkers for efficacy and adverse events in immune checkpoint inhibitor therapy (Review).Molecular medicine reports · 2026Review
- Epstein-Barr virus-encoded microRNA-BART17-5p suppresses cell proliferation and metastasis by targeting CERK.PLoS pathogens · 2026Article
- Downregulation of GSDMB by EBV-encoded miR-BART12-3p suppresses killer lymphocyte-mediated pyroptosis in gastric cancer cells.PLoS pathogens · 2026Article
- Epstein-Barr virus-encoded microRNAs: central players in nasopharyngeal and gastric carcinoma pathogenesis.Archives of virology · 2026Review
- Epstein-Barr virus and human MiRNAs crosstalk: orchestrating latency, lytic cycle, and immune system modulation.Folia microbiologica · 2026Review
- Long noncoding RNA ADEI/miR-93-3p/STAT3 axis promotes Epstein-Barr virus-positive diffuse large B-cell lymphoma progression and immune evasion through regulating the PD-1/PD-L1 checkpoint.Cell death & disease · 2026Article
- STAT3 at the tumor-immune interface: mechanisms of immune escape and therapeutic opportunities.Frontiers in immunology · 2026Review
- The microbiome-EBV axis in carcinogenesis bridges commensal influence and viral oncogenesis.Frontiers in immunology · 2026Review
- CD8 + T Cells in Gastrointestinal Cancer: a Perspective on Targeting MicroRNA.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Epstein-Barr virus-coded miR-BART19-3p promotes proliferation of EBV-associated gastric cancer by inhibiting GADD45B.Journal of translational medicine · 2025Article
- Review
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Prognostic and immunological implications of protein kinases in gastric cancer: a focus on hub gene ABL2 and its impact on the polarization of M2 macrophages.Biology direct · 2025Article
- Recent advances in the mechanisms of PD-L1 expression in gastric cancer: a review.Biological research · 2025Review
- Non-coding RNAs as potential mediators of resistance to lung cancer immunotherapy and chemotherapy.Oncology research · 2025Review
- Classical biomarkers and non-coding RNAs associated with diagnosis and treatment in gastric cancer.Oncology research · 2025Review
- EBV-miR-BART5-5p regulates RORA to promote proliferation and migration of gastric cancer cells.PloS one · 2025Article
- Implications of EBV-Encoded and EBV-Related miRNAs in Tumors.Current gene therapy · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEpstein-Barr virus (EBV) is etiologically associated with ~ 10% of all gastric carcinomas. However, the molecular mechanisms and roles of EBV miRNAs in gastric carcinoma oncogenesis are yet to be elucidated.
methodsMicroRNA microarray and TaqMan quantitative real-time RT-PCR were conducted. RT-PCR and luciferase reporter assay for PIAS3, western blotting for 20 proteins, immunofluorescence for STAT3, transfection with miRBART5-5p-plasmid, STAT3-plasmid, miRBART5-5p mimic, or PIAS3-siRNA, and in vitro assays for biological effects of PD-L1 were implemented. In situ hybridization for EBV-encoded small RNAs and immunohistochemistry were performed on gastric carcinoma tissues.
resultsTransfecting miR-BART5-5p into EBV(-) gastric carcinoma cell lines caused a decrease in PIAS3 3'-UTR reporter activity, PIAS3 downregulation, and subsequent STAT3 activation followed by PIAS3/pSTAT3-dependent PD-L1 upregulation. Interestingly, due to PD-L1 knockdown, apoptosis was increased, while the rate of cell proliferation, invasion capacity, and migration were decreased in miR-BART5-5p-transfected cells. In EBV(+) gastric carcinoma cells, anti-miR-BART5-5p reduced PD-L1 levels through PIAS3/pSTAT3 control. Among 103 patients with EBV-associated gastric carcinomas, overall survival was significantly shortened for those with PD-L1(+) tumors compared to those with PD-L1(-) tumors (P = 0.049).
conclusionsOur findings imply that miR-BART5-5p directly targets PIAS3 and augments PD-L1 through miR-BART5/PIAS3/pSTAT3/PD-L1 axis control. This contributes to antiapoptosis, tumor cell proliferation, invasion and migration, as well as immune escape, furthering gastric carcinoma progression and worsening the clinical outcome, especially in the PD-L1(+) group of patients with EBV-associated gastric carcinomas. miR-BART5-5p may, therefore, be amenable to PD-1/PD-L1 immune checkpoint inhibitor therapy.
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