{
  "abstract": "Context\n\nType 2 diabetes (T2D) markedly increases the risk of cardiovascular disease (CVD). Circulating microRNAs (miRNAs) are promising biomarkers for patient stratification and may provide mechanistic insight into dysregulated pathways in T2D-associated CVD.Objective\n\nThis work aimed to identify circulating miRNA signatures in T2D patients with CVD (T2D-CVD) vs T2D patients without CVD using a novel network-based medicine approach.Methods\n\nPatients (n = 110) were stratified into T2D and T2D-CVD groups based on the absence or presence of macrovascular complications. Circulating miRNAs, proinflammatory cytokines, and growth factors were profiled in a discovery cohort (n = 80) and confirmed in a validation cohort (n = 30). Differential expression, network-based approaches, and pathway enrichment analyses identified miRNA signatures, coexpression communities, hub miRNAs, and associated signaling pathways.Results\n\nT2D-CVD patients showed a set of elevated inflammatory cytokines and circulating miRNAs. Particularly, 19 miRNAs were differentially expressed between T2D-CVD and T2D patients. Pathway enrichment of these miRNAs highlighted Hippo signaling together with transforming growth factor-β, mechanistic target of rapamycin, Wnt, and PI3K-Akt pathways. Network analysis identified a coexpression community of 34 miRNAs, including hub miRNAs let-7a-5p, miR-132-3p, and miR-1306-3p, all linked to Hippo signaling. Key miRNA interactions were validated, and differentially expressed and hub miRNAs both correlated with inflammatory mediators such as PAR-1, CXCL1, and NEMO, which are linked to Hippo pathway regulation.Conclusion\n\nThis study identified a network of circulating miRNAs associated with inflammatory cytokines and Hippo signaling pathway in T2D-CVD. These findings reveal novel molecular aspects of the systemic inflammation characterizing T2D-CVD and support the potential of Hippo-related circulating miRNAs as mechanistic biomarkers for cardiovascular risk in T2D.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Experimental Medicine, Sapienza University of Rome, Rome 00161, Italy.",
    "Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.",
    "Department of Public Health Sciences, University of Miami, Miami, FL 33136, USA.",
    "Max Delbrück Center-Berlin Institute for Medical Systems Biology (MDC-BIMSB), Berlin 10115, Germany.",
    "Department of Medicine, Surgery and Neuroscience, University of Siena, Siena 53100, Italy.",
    "Department of Computer, Control and Management Engineering, Sapienza University of Rome, Rome 00161, Italy.",
    "Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.",
    "Department of Life, Health and Health Professions Sciences, Link Campus University, Rome 00165, Italy.",
    "Laboratory of Preclinical and Translational Research, IRCCS CROB Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, PZ 85028, Italy.",
    "Department of Radiological, Oncological & Pathological Sciences, Sapienza University of Rome, Rome 00161, Italy.",
    "Department of Systems Medicine, Tor Vergata University, Rome 00133, Italy.",
    "Department of Medicine, University of Padova, Padua 35121, Italy.",
    "Department of Biomedical Science, Consiglio Nazionale delle Ricerche, Rome 00185, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zein Mersini Besharat",
      "orcid": "0000-0003-0317-9854"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Sofia Trocchianesi",
      "orcid": "0000-0002-8157-2638"
    },
    {
      "affs": [
        4
      ],
      "name": "Giuseppina Emanuela Grieco",
      "orcid": "0000-0001-7325-6128"
    },
    {
      "affs": [
        0
      ],
      "name": "Tanja Milena Autilio",
      "orcid": "0000-0003-4092-1990"
    },
    {
      "affs": [
        5
      ],
      "name": "Caterina Alfano",
      "orcid": "0000-0002-7296-8112"
    },
    {
      "affs": [
        6
      ],
      "name": "Angela Dardano"
    },
    {
      "affs": [
        4
      ],
      "name": "Daniela Fignani",
      "orcid": "0000-0001-8803-5846"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Splendiani",
      "orcid": "0000-0003-4259-9093"
    },
    {
      "affs": [
        7
      ],
      "name": "Anna Citarella",
      "orcid": "0000-0003-1290-4990"
    },
    {
      "affs": [
        8
      ],
      "name": "Claudia Sabato",
      "orcid": "0000-0001-7533-4660"
    },
    {
      "affs": [
        7
      ],
      "name": "Zaira Spinello",
      "orcid": "0000-0002-7016-6538"
    },
    {
      "affs": [
        7
      ],
      "name": "Giuseppina Catanzaro",
      "orcid": "0000-0001-8427-9691"
    },
    {
      "affs": [
        9
      ],
      "name": "Agnese Po",
      "orcid": "0000-0002-9346-8782"
    },
    {
      "affs": [
        5
      ],
      "name": "Manuela Petti",
      "orcid": "0000-0002-0149-161X"
    },
    {
      "affs": [
        5
      ],
      "name": "Lorenzo Farina",
      "orcid": "0000-0001-8314-6029"
    },
    {
      "affs": [
        0
      ],
      "name": "Mary Anna Venneri",
      "orcid": "0000-0002-0687-8135"
    },
    {
      "affs": [
        10
      ],
      "name": "Davide Lauro",
      "orcid": "0000-0002-8597-4415"
    },
    {
      "affs": [
        11
      ],
      "name": "Gian Paolo Fadini",
      "orcid": "0000-0002-6510-2097"
    },
    {
      "affs": [
        4,
        12
      ],
      "name": "Francesco Dotta",
      "orcid": "0000-0003-4947-7478"
    },
    {
      "affs": [
        4
      ],
      "name": "Guido Sebastiani",
      "orcid": "0000-0003-4374-8564"
    },
    {
      "affs": [
        6
      ],
      "name": "Andrea Natali",
      "orcid": "0000-0002-8465-7717"
    },
    {
      "affs": [
        10
      ],
      "name": "Elisabetta Ferretti",
      "orcid": "0000-0001-7265-6429"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6zqnyg1qskadp.bib",
  "cited_by": 0,
  "doi": "10.1210/jendso/bvag229",
  "fulltext_url": "https://europepmc.org/articles/PMC13684395",
  "id": "6zqnyg1qskadp",
  "issns": [
    "2472-1972"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909870",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|MicroRNA in disease regulation"
    ]
  ],
  "openalex": "W7221788308",
  "pdf_url": "https://europepmc.org/articles/PMC13684395?pdf=render",
  "pmcid": "PMC13684395",
  "pmid": "42909870",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6zqnyg1qskadp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42909870",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909870"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|MicroRNA in disease regulation",
      "subfield": "oncology"
    }
  ],
  "title": "Hippo signaling-linked circulating microRNA networks are associated with cardiovascular disease in type 2 diabetes.",
  "title_text": "Hippo signaling-linked circulating microRNA networks are associated with cardiovascular disease in type 2 diabetes.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/6zqnyg1qskadp",
  "venue": "Journal of the Endocrine Society",
  "versions": []
}