{
  "abstract": "Introduction: Circular RNAs (circRNAs) have emerged as important regulators of diverse cellular processes, and accumulating evidence indicates that certain circRNAs modulate immune responses through complex mechanisms. However, their roles in innate immunity against influenza A virus (IAV) infection remain poorly understood.\n\nMethods: We identified a previously uncharacterized circRNA, termed circMARCH3, through RNA-seq, RNase R digestion assay, and RNA stability assay. We examined circMARCH3 expression in multiple cell types following viral infection by RT-PCR and real-time PCR, investigated the signaling pathway driving its induction, and performed functional analyses using circMARCH3 overexpression vectors and shRNAs-mediated knockdown. Furthermore, we identified and validated the circMARCH3/miR-3657/ATG7 axis through mechanistic studies.\n\nResults: circMARCH3 is generated from the pre-mRNA of the membrane-associated RING-CH-Type Finger 3 (MARCH3) gene, and its expression was robustly induced by IAV and several other viral infections in multiple cell types. Mechanistically, virus-induced circMARCH3 expression was driven by the NF-κB signaling pathway. Functional analyses demonstrated that circMARCH3 overexpression significantly promoted IAV replication, whereas circMARCH3 knockdown markedly inhibited viral production. Consistent with these findings, circMARCH3 functioned as a negative regulator of antiviral innate immunity by attenuating NF-κB activation and type I interferon responses. Furthermore, we identified that circMARCH3 targeted miR-3657, a microRNA that suppresses the expression of ATG7, a key autophagy regulator and known pro-IAV factor. Mechanistic studies revealed that circMARCH3 acted as a competitive endogenous RNA (ceRNA), sequestering miR-3657 and thereby relieving its repressive effect on ATG7 expression, resulting in enhanced autophagy and increased viral replication.\n\nDiscussion: The results demonstrate circMARCH3 as a virus-inducible circRNA that promotes IAV infection through two complementary mechanisms: dampening NF-κB-mediated antiviral innate immunity and facilitating autophagy via the circMARCH3/miR-3657/ATG7 axis. Our findings establish circMARCH3 as a novel regulator of the complex interaction between host and IAV by coordinating NF-κB negative feedback and the miR-3657/ATG7 axis.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Science, Fujian Agriculture and Forestry University",
    "Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Science, Fujian Agriculture and Forestry University",
    "Joint Laboratory of Animal Pathogen Prevention and Control of Fujian-Nepal, College of Animal Science, Fujian Agriculture and Forestry University",
    "Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
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        0,
        1,
        2
      ],
      "name": "Jiayin Liu"
    },
    {
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        1,
        2
      ],
      "name": "Jiarong Song"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ling’en Yang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohamed Maarouf"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Haori Qiu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Shasha Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Shile Huang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Song Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ji-Long Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4x126wq06acw0.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1948323",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736778/",
  "id": "4x126wq06acw0",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948323/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1312|Circular RNAs in diseases"
    ]
  ],
  "openalex": "W7223168423",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1948323/pdf",
  "pmcid": "PMC13736778",
  "pmid": "42991784",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4x126wq06acw0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1948323",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948323/full"
    },
    {
      "first_seen": "2026-11-09T12:22:09Z",
      "native_id": "PMC13736778",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1948323"
    }
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Circular RNAs in diseases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Circular RNA MARCH3 promotes influenza A virus replication by coordinating NF-κB negative feedback and the miR-3657/ATG7 axis",
  "title_text": "Circular RNA MARCH3 promotes influenza A virus replication by coordinating NF-κB negative feedback and the miR-3657/ATG7 axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:09Z",
  "url": "https://research.draconitic.com/paper/4x126wq06acw0",
  "venue": "Frontiers in Immunology",
  "versions": []
}