{
  "abstract": "Background: Autism Spectrum Disorder (ASD) remains poorly understood in molecular pathogenesis, and lacks reliable peripheral biomarkers and targeted interventions.\n\nObjective: This study aimed to identify cross-omics molecular signatures and core regulatory pathways in ASD by integrating serum transcriptomic and proteomic data from children with ASD and typically developing (TD) children.\n\nMethods: Serum transcriptomics and label-free data-independent acquisition (label-free DIA) quantitative proteomics were analyzed in 13 children with ASD and 13 age- and sex-matched TD controls. Differential expression analysis, functional enrichment, and two-way orthogonal partial least squares (O2PLS) multi-omics integration were performed. A valproic acid (VPA)-induced SH-SY5Y neuronal differentiation model was used to preliminarily validate the expression patterns of the Hippo signaling pathway and its downstream molecular events.\n\nResults: We identified 6,563 differentially expressed genes (DEGs, 94.2% upregulated) and 157 differentially expressed proteins (DEPs, 75.2% downregulated), which demonstrated widespread post-transcriptional dysregulation in ASD serum. Functional enrichment analyses highlighted aberrations in energy metabolism, ciliary function, and chemical perception. O2PLS integration nominated Fibronectin-1 (FN1) as a pivotal cross-omics target, with elevated transcription but reduced protein abundance. The Hippo signaling pathway emerged as a central regulatory hub, with core its components significantly downregulated at the mRNA level. In vitro experiments revealed that VPA-triggered neuronal dysregulation was accompanied by Hippo pathway gene suppression, FN1 transcriptional upregulation, and selective induction of interleukin-6 (IL-6), suggesting a putative Hippo-FN1-IL-6 regulatory axis.\n\nConclusion: Post-transcriptional dysregulation represents a prominent molecular feature of ASD serum. The proposed Hippo-FN1-IL-6 cascade may provide a mechanistic link between developmental signaling defects and neuroinflammation in ASD pathogenesis. FN1 holds potential as a candidate diagnostic biomarker and therapeutic target, yet its clinical utility and the underlying detailed regulatory mechanisms require further validation in independent large-scale cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Shandong Provincial Maternal and Child Health Care Hospital affiliated to Qingdao University, Qingdao University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ziyun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Mai Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ting Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lu Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dawei Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Qian Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Huijuan Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lihong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/80n3t7yrv8h6j.bib",
  "cited_by": 0,
  "doi": "10.3389/fpsyt.2026.1978167",
  "fulltext_url": null,
  "id": "80n3t7yrv8h6j",
  "issns": [
    "1664-0640"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1978167/full",
  "language": null,
  "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": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/80n3t7yrv8h6j.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:44Z",
      "native_id": "10.3389/fpsyt.2026.1978167",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1978167/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1664-0640",
      "subfield": "psychiatry"
    }
  ],
  "title": "The potential core role of the FN1-Hippo signaling axis in the pathological mechanism of autism spectrum disorder",
  "title_text": "The potential core role of the FN1-Hippo signaling axis in the pathological mechanism of autism spectrum disorder",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:44Z",
  "url": "https://research.draconitic.com/paper/80n3t7yrv8h6j",
  "venue": "Frontiers in Psychiatry",
  "versions": []
}