{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:29:19Z","timestamp":1785540559794,"version":"3.56.0"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["No.82460561"],"award-info":[{"award-number":["No.82460561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumors","award":["No:2022NHCDP2022005"],"award-info":[{"award-number":["No:2022NHCDP2022005"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Epstein-Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subtype of gastric cancer. EBV encodes various viral RNAs, including BamHI-A rightward transcripts (BARTs), which are implicated in the carcinogenic processes of EBVaGC. This study aims to explore the function and underlying mechanisms of EBV-miR-BART5-5p in gastric cancer, providing a basis for the identification of more effective biomarkers for EBVaGC.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Gene expression data were first downloaded from the GSE51575 dataset to identify differentially expressed genes and construct a WGCNA network, which led to the identification of RORA as a key gene associated with EBV-miR-BART5-5p. We then analyzed the TCGA dataset to investigate the differential expression and prognostic significance of RORA in gastric cancer. Further analysis explored RORA\u2019s enriched pathways and its relationship with immune response, tumor mutation burden, and drug sensitivity. Single-cell gene expression characteristics of RORA were assessed using the GSE134520 dataset. RT-qPCR was employed to determine RORA expression levels in both EBV-positive and -negative gastric cancer cell lines. Western blotting and dual-luciferase reporter assays confirmed the targeting of RORA\u2019s 3\u2019 UTR by EBV-miR-BART5-5p. Finally, a series of functional experiments demonstrated that EBV-miR-BART5-5p promotes proliferation and migration of both EBV-positive and -negative gastric cancer cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In this study, differential expression and WGCNA analyses identified 910 co-expressed genes. We then investigated miR-BART5-5p in EBV-positive gastric cancer and identified RORA as a potential target gene. Our analysis revealed that RORA expression is lower in tumor samples compared to normal samples, and single-cell analysis showed significant upregulation of RORA in CD8\u2009+\u2009T cells. Experimental data further demonstrated that RORA is expressed at lower levels in EBV-positive gastric cancer cell lines and that EBV-miR-BART5-5p targets the 3\u2019 UTR of RORA. This suggests that EBV-miR-BART5-5p may promote gastric cancer cell proliferation and migration by regulating RORA.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our study reveals the molecular characteristics of EBV-associated gastric cancer, establishes a prognostic model for RORA in gastric cancer, and demonstrates that EBV-miR-BART5-5p may target and inhibit RORA to promote gastric cancer cell proliferation and migration. These findings highlight EBV-miR-BART5-5p could serve as a diagnostic biomarker and a potential therapeutic target for gastric cancer.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0327323","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T17:54:29Z","timestamp":1752170069000},"page":"e0327323","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["EBV-miR-BART5-5p regulates RORA to promote proliferation and migration of gastric cancer 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