{
  "abstract": "Alternative splicing (AS) is a fundamental post-transcriptional mechanism that vastly expands transcriptomic and proteomic diversity, with approximately 95% of human multi-exon genes generating alternatively spliced transcripts. This process is tightly regulated in a tissue- and developmental stage-specific manner, and its dysregulation is increasingly recognized as a hallmark of cancer. The U2 auxiliary factor (U2AF) heterodimer, composed of the small subunit U2AF1 and the large subunit U2AF2, plays a critical rate-limiting role in early spliceosome assembly by mediating 3’ splice site recognition and U2 snRNP recruitment. While U2AF1 has been extensively characterized in hematological malignancies and solid tumors, its binding partner U2AF2 has received comparatively less systematic attention, despite being equally indispensable for splicing fidelity. This review synthesizes current knowledge on U2AF2’s structural architecture, its multifaceted oncogenic functions, and the mutational landscape that underpins its pathological contributions to cancer. We examine how U2AF2 operates as a molecular integrator, coupling oncogenic signals to transcriptomic remodeling, metabolic reprogramming, and therapeutic resistance through both canonical splicing-dependent and non-canonical mechanisms. We further review emerging therapeutic strategies targeting U2AF2, including small-molecule inhibitors, spliceosome modulators, approaches targeting downstream non-coding RNA effectors, and immunotherapeutic modalities that exploit U2AF2 overexpression as a tumor-associated antigen. Finally, we discuss the clinical potential and translational challenges of these strategies and outline future directions for harnessing U2AF2 biology in precision oncology.",
  "abstract_shown": true,
  "affiliations": [
    "School of Basic Medical Sciences & School of Public Health, Faculty of Medicine, Yangzhou University",
    "Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control, Yangzhou University",
    "Department of Clinical Pharmacy, The People’s Hospital of Jiaozuo"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Han Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yi Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinyuan Lin"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hua Dai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shengzhe Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/40j7az2n38w50.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1991483",
  "fulltext_url": null,
  "id": "40j7az2n38w50",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1991483/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/40j7az2n38w50.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:33Z",
      "native_id": "10.3389/fimmu.2026.1991483",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1991483/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "U2AF2 as a regulatory hub in cancer: linking spliceosome dysregulation, metabolic reprogramming, and non-coding RNA networks to targeted therapy",
  "title_text": "U2AF2 as a regulatory hub in cancer: linking spliceosome dysregulation, metabolic reprogramming, and non-coding RNA networks to targeted therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:33Z",
  "url": "https://research.draconitic.com/paper/40j7az2n38w50",
  "venue": "Frontiers in Immunology",
  "versions": []
}