{
  "abstract": "Background: Keloids are fibroproliferative scars characterized by persistent inflammation, aberrant wound healing, and excessive extracellular matrix deposition. Although dysregulated miRNAs have been reported in keloids, their links to disease susceptibility and downstream fibrotic pathways remain incompletely defined.\n\nMethods: We integrated miRNA-QTL-based Mendelian randomization with differential expression analysis of GSE237753 to prioritize keloid-associated miRNAs. Targets of miR-539-3p were screened using miRTarBase, miRDB, and TargetScan, followed by functional annotation and literature-guided prioritization. miR-539-3p and SOX9 expression were assessed by qRT-PCR in eight paired primary normal skin-derived and keloid-derived fibroblast samples, and SOX9 protein expression was examined by immunohistochemistry in 20 independent tissue specimens. SOX9-centered networks were constructed using STRING and GeneMANIA, followed by Gene Ontology and KEGG enrichment analyses. SOX9 mRNA and protein were also measured after miR-539-3p inhibitor treatment.\n\nResults: Mendelian randomization identified nine miRNAs nominally associated with keloid susceptibility, but none remained significant after FDR correction. miR-539-3p showed a nominal inverse association and was the only miRNA overlapping with the differential expression results. In paired primary fibroblasts, both miR-539-3p and SOX9 expression were higher in keloid-derived cells (P = 3.69 × 10−5 and P = 1.09 × 10−5, respectively). SOX9 immunohistochemistry showed stronger staining in keloid tissue specimens (P = 5.18 × 10−5). SOX9 mRNA and protein were higher after inhibitor treatment than after negative-control treatment in three independent experiments per assay. Network analyses linked SOX9 to extracellular matrix organization, connective tissue development, Notch signaling, and TGF-β/Wnt-related remodeling.\n\nDiscussion: The genetic analysis focused on genetically predicted circulating miR-539-3p levels, whereas the expression data came from established keloid tissues and derived fibroblasts. These findings reflect different biological contexts, and their different directions are not necessarily contradictory. The increase in SOX9 after miR-539-3p inhibitor treatment warrants further investigation of its potential regulation by miR-539-3p,but does not establish direct targeting in keloid fibroblasts. The expression and network findings provide a rationale for studying whether SOX9 contributes to fibroblast activation and extracellular matrix production in keloids.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Dermatology, Yanbian University Hospital, Yanbian University Medical College, Yanji, China",
    "Keloid Research Center, Department of Dermatology, Yanbian University Medical College, Yanji, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhanpeng Luo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ling Ge"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lili Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shaoyou Lin"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tianhui Wei"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bo Lu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhehu Jin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ch56ketxekxvh.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1931861",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731340/",
  "id": "ch56ketxekxvh",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1931861",
  "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",
      "2708|Dermatologic Treatments and Research"
    ]
  ],
  "openalex": "W7223094467",
  "pdf_url": "https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1931861/pdf",
  "pmcid": "PMC13731340",
  "pmid": "42985007",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ch56ketxekxvh.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:33Z",
      "native_id": "PMC13731340",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1931861"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2708|Dermatologic Treatments and Research",
      "subfield": "general"
    }
  ],
  "title": "Integrated genetic and transcriptomic analyses suggest a miR-539-3p/SOX9-associated expression pattern in keloids",
  "title_text": "Integrated genetic and transcriptomic analyses suggest a miR-539-3p/SOX9-associated expression pattern in keloids",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:33Z",
  "url": "https://research.draconitic.com/paper/ch56ketxekxvh",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}