{
  "abstract": "Epstein-Barr virus (EBV) is an oncogenic DNA virus that is etiologically associated with multiple malignancies, including nasopharyngeal carcinoma, gastric carcinoma, and lymphomas. Although EBV encodes numerous viral microRNAs (miRNAs), the pathogenic functions of individual miRNAs remain incompletely characterized. In this study, we identify EBV-encoded miR-BART17-5p as a tumor-suppressive miRNA that directly targets ceramide kinase (CERK). CERK expression is significantly downregulated in EBV-associated gastric cancer (EBVaGC) tissues and EBV-positive AGS-EBV cells and inversely correlates with miR-BART17-5p levels. Mechanistic analyses further demonstrate that miR-BART17-5p directly targets the 3′ untranslated region (3′UTR) of CERK, thereby regulating its expression. Overexpression of miR-BART17-5p mimics or knockdown of CERK in AGS cells significantly suppresses tumor -associated phenotypes, including cell proliferation, migration, and invasion. Conversely, inhibition of miR-BART17-5p in AGS-EBV cells rescues these phenotypes. Similar results were obtained in SNU719 cells. Mechanistically, miR-BART17-5p inhibits the PI3K/AKT signaling by targeting CERK. Restoration of CERK expression reactivates PI3K/AKT signaling and reverses the inhibitory effects on cell proliferation, migration, and invasion in AGS cells. To evaluate the therapeutic potential of miR-BART17-5p, systemic administration of engineered cholesterol-conjugated miR-BART17-5p agomirs significantly suppresses tumor growth in xenograft models. Collectively, our findings reveal a previously unrecognized EBV-host interaction whereby miR-BART17-5p constrains cancer progression through modulation of CERK/PI3K/AKT signaling activation, highlighting its potential as a preclinical therapeutic strategy for cancer. Author summary: Epstein-Barr virus (EBV) is a common virus that infects most people worldwide and is linked to several types of cancer, including cancers of the stomach, nose, and blood system. Although this virus produces many small regulatory molecules, microRNAs, the roles of many of these molecules in cancer development remain unclear. In this study, we investigated the function of one viral microRNA, known as miR-BART17-5p, and its impact on cancer progression. We found that miR-BART17-5p acts as a natural brake on cancer growth by reducing the activity of a host protein, ceramide kinase (CERK), which normally promotes signals that support cell growth and spread. When levels of miR-BART17-5p were increased, cells grew more slowly and were less able to move and invade surrounding tissues. In contrast, blocking this microRNA restored aggressive cancer behaviors. We also showed that restoring miR-BART17-5p in animal models using a chemically modified mimic significantly reduced tumor growth. Our findings reveal an unexpected way in which a virus can restrain cancer development by regulating host cell signaling. This work improves our understanding of virus-host interactions and suggests that viral microRNAs may be developed as candidate molecules for future therapeutic development in cancers associated with EBV.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China",
    "Department of paediatrics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China",
    "Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Peilin Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiazhen Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiong Wu"
    },
    {
      "name": "Lu Zhang"
    },
    {
      "name": "Fan Xin"
    },
    {
      "name": "Xiaowei Zheng"
    },
    {
      "name": "Xu Lin"
    },
    {
      "name": "Wannan Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/28yx4tj2d7axf.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014519",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014519",
  "id": "28yx4tj2d7axf",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014519",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|MicroRNA in disease regulation"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Natural antisense transcripts/MicroRNAs"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell proliferation"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Signal inhibition"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/MicroRNAs"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Carcinoma/Nasopharyngeal carcinoma"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Gastric cancer"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ]
  ],
  "openalex": "W7213305704",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014519&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/28yx4tj2d7axf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.ppat.1014519",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014519"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "plos:cancers and neoplasms",
      "subfield": "oncology"
    }
  ],
  "title": "Epstein-Barr virus-encoded microRNA-BART17-5p suppresses cell proliferation and metastasis by targeting CERK",
  "title_text": "Epstein-Barr virus-encoded microRNA-BART17-5p suppresses cell proliferation and metastasis by targeting CERK",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/28yx4tj2d7axf",
  "venue": "PLOS Pathogens",
  "versions": []
}