{
  "abstract": "The fibrotic subtype of the tumor microenvironment characterized by epithelial-mesenchymal transition, fibrosis, angiogenesis and immune exclusion, predicts poor outcomes across diverse malignancies, yet the role of miR-145 in this context remains unexplored. Leveraging The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) and breast cancer (BRCA) databases, we demonstrate that miR-145 reprogramming recapitulates a noninflamed fibrotic phenotype with immune exclusion. In high miR-145 tumors, EMT programs persist alongside abundant cancer-associated fibroblasts, matrix remodeling and angiogenesis, with upregulation of NOTCH, TGF-β, myogenesis, hypoxia, Hedgehog, and Wnt/β-catenin signaling and downregulation of interferon-γ and JAK–STAT pathways. Our findings illustrate that cancer–stromal juxtacrine interactions activate NOTCH signaling, forming a positive feedback loop that amplifies miR-145 expression and is reinforced by miR-145 promoter hypomethylation. High miR-145 promotes autophagy and mitochondrial oxidative phosphorylation (OXPHOS) metabolism in cancer cells, with GAPDH serving as a central hub linking metabolism, noninflamed immune modulation, and poor clinical outcomes. In vivo, high miR-145 carcinoma cells co-engrafted with fibroblasts drive tumor growth through enhanced metabolism, angiogenesis and immune evasion. This study establishes miR-145 as a driver and biomarker of the fibrotic tumor microenvironment to better inform future cancer therapy strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States",
    "Department of Otolaryngology, Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhao Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Megan Bennett"
    },
    {
      "affs": [
        1
      ],
      "name": "Patrick Tassone"
    },
    {
      "affs": [
        1
      ],
      "name": "Joseph M. Curry"
    },
    {
      "affs": [
        0
      ],
      "name": "Ubaldo Martinez-Outschoorn"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9b53xxtw9wp52.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1850756",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737585/",
  "id": "9b53xxtw9wp52",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1850756",
  "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",
      "1306|MicroRNA in disease regulation"
    ]
  ],
  "openalex": "W7222984977",
  "pdf_url": "https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1850756/pdf",
  "pmcid": "PMC13737585",
  "pmid": "42992022",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9b53xxtw9wp52.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:44Z",
      "native_id": "PMC13737585",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1850756"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|MicroRNA in disease regulation",
      "subfield": "oncology"
    }
  ],
  "title": "MiR-145 reprogramming facilitates fibrotic trajectory in the tumor microenvironment",
  "title_text": "MiR-145 reprogramming facilitates fibrotic trajectory in the tumor microenvironment",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:44Z",
  "url": "https://research.draconitic.com/paper/9b53xxtw9wp52",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}