{
  "abstract": "BackgroundPIK3CA-related overgrowth spectrum (PROS) is a group of disorders caused by somatic mosaic mutations in the PIK3CA gene, characterized by tissue overgrowth affecting multiple organs, including the skin, adipose tissue, blood vessels, bones, and nervous system. Although constitutive hyperactivation of PI3K-AKT-mTOR signaling in PROS promotes abnormal tissue development, remodeling, and segmental overgrowth, the downstream signaling networks are highly complex, and the precise molecular mechanisms underlying tissue overgrowth remain incompletely understood.MethodsIn this exploratory study, we investigated molecular alterations associated with overgrowth in PROS by profiling mRNA and microRNA expression in fibroblasts derived from affected skin (pv-Fibro) and unaffected skin (non-pv-Fibro) from the same patient. Additionally, fibroblasts from three healthy individuals were pooled and analyzed as a single control sample.ResultsWe identified 24,034 human mRNAs using microarray-based gene expression profiling. Ten mRNAs were selected as candidate lesion-associated upregulated genes in pv-Fibro (≥5-fold vs. nc-Fibro and <2-fold change in non-pv-Fibro vs. nc-Fibro). In contrast, three mRNAs were selected as candidate lesion-associated downregulated genes in pv-Fibro (≤0.2-fold vs. nc-Fibro and >0.5-fold in non-pv-Fibro vs. nc-Fibro). For miRNA profiling, 4,603 human microRNAs were analyzed. hsa-miR-146a-5p was markedly upregulated in pv-Fibro (≥5-fold vs. nc-Fibro and <2-fold change in non-pv-Fibro vs. nc-Fibro), while hsa-miR-146b-5p was markedly downregulated (≤0.2-fold vs. nc-Fibro and >0.5-fold in non-pv-Fibro vs. nc-Fibro).DiscussionThe observed changes in mRNA and miRNA expression represent candidate molecular alterations associated with inflammatory and tissue remodeling pathways in PROS pathology.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan",
    "Department of Pediatrics, International University of Health and Welfare Narita Hospital, Narita, Japan",
    "Department of Neurology, Mayo Clinic, Rochester, MN, United States",
    "Department of Plastic, Reconstructive, and Aesthetic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan",
    "Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan",
    "Department of Pediatrics, Showa Medical University School of Medicine, Tokyo, Japan",
    "Department of Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan",
    "Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tadashi Shiohama"
    },
    {
      "affs": [
        1
      ],
      "name": "Tadashi Shiohama"
    },
    {
      "affs": [
        2
      ],
      "name": "Mami Uegami"
    },
    {
      "affs": [
        3
      ],
      "name": "Yoshitaka Kubota"
    },
    {
      "affs": [
        4
      ],
      "name": "Hirotomo Saitsu"
    },
    {
      "affs": [
        5
      ],
      "name": "Mitsuhiro Kato"
    },
    {
      "affs": [
        6
      ],
      "name": "Jun Matsushima"
    },
    {
      "affs": [
        7
      ],
      "name": "Jun Matsushima"
    },
    {
      "affs": [
        0
      ],
      "name": "Daisuke Sawada"
    },
    {
      "affs": [
        0
      ],
      "name": "Shoko Yoshii"
    },
    {
      "affs": [
        3
      ],
      "name": "Nobuyuki Mitsukawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiromichi Hamada"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cheyk0rsy83ss.bib",
  "cited_by": 0,
  "doi": "10.3389/fgene.2026.1935186",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fgene.2026.1935186/full",
  "id": "cheyk0rsy83ss",
  "issns": [
    "1664-8021"
  ],
  "landing_url": "https://doi.org/10.3389/fgene.2026.1935186",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH426-470"
    ],
    [
      "openalex",
      "2746|Vascular Malformations and Hemangiomas"
    ]
  ],
  "openalex": "W7223213277",
  "pdf_url": "https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1935186/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/cheyk0rsy83ss.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:03Z",
      "native_id": "3d436508a1164836bf2c6f50a7119d0d",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fgene.2026.1935186"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Vascular Malformations and Hemangiomas",
      "subfield": "surgery"
    }
  ],
  "title": "Exploratory mRNA and microRNA profiling identifies transcriptomic alterations in the PIK3CA-related overgrowth spectrum",
  "title_text": "Exploratory mRNA and microRNA profiling identifies transcriptomic alterations in the PIK3CA-related overgrowth spectrum",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:03Z",
  "url": "https://research.draconitic.com/paper/cheyk0rsy83ss",
  "venue": "Frontiers in Genetics",
  "versions": []
}