{
  "abstract": "DDX3 has dual biological functions of regulating cell proliferation and antiviral effects. Herein, we focus on SUMOylation‐mediated DDX3 in the interplay from hepatitis B virus (HBV) infection to HBV‐associated hepatocellular carcinoma (HBV‐HCC) progression. We identified dynamic regulation of SUMOylation and DeSUMOylation of DDX3 at four key lysine (K) residues (K81/K208/K215/K564) in response to HBV infection. During the early stage of HBV acute infection, SENP1 interacts with DDX3 to keep DDX3 deSUMOylation for inhibiting HBV replication. During persistent HBV replication, as SENP1 downregulation and HBV polymerase accumulation, DDX3 disassociates with SENP1 to bind with TRIM28, which induces DDX3 SUMOylation. Meanwhile, SUMOylated DDX3 enhances alternative splicing of KLF4 mRNAs to generate KLF4α isoform that involves in Cyclin D1‐mediated cell cycle progression, weakens tumor suppressor function of DDX3 and promotes HBV‐HCC. Moreover, DDX3 expression is positively correlated with KLF4 mRNA, and high DDX3 level with low TRIM28 expression indicates a better overall survival for HBV‐HCC patients. Our findings reveal the dynamic regulation between SUMOylation and deSUMOylation of DDX3, including mediating HBV gene transcription, virus antigen secretion, and cell proliferation. Furthermore, the TRIM28‐DDX3‐KLF4 axis as a novel therapeutic target for HBV‐HCC, exhibiting the dual ability to inhibit tumor progression and disrupt the HBV–host interaction.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China",
    "Department of Central Laboratory NHC Key Laboratory of Pulmonary Immunological Diseases Guizhou Provincial People's Hospital Guiyang China",
    "Department of Neurology Second Affiliated Hospital of Army Medical University (Xinqiao Hospital) Chongqing China",
    "Department of Medical Oncology Cancer Center West China Hospital Sichuan University Chengdu China",
    "Department of Gastrointestinal Surgery West China Hospital Sichuan University Chengdu China",
    "The Second Department of Gastrointestinal Surgery the Affiliated Hospital of North Sichuan Medical College Sichuan China",
    "Department of Biochemistry and Biotechnology Baghdad Campus The Islamia University of Bahawalpur Bahawalpur Pakistan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yanfang Yang",
      "orcid": "0000-0002-3676-1616"
    },
    {
      "affs": [
        0
      ],
      "name": "Ting Kong"
    },
    {
      "affs": [
        2
      ],
      "name": "Binghan Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoli Jin",
      "orcid": "0000-0002-5039-1850"
    },
    {
      "affs": [
        0
      ],
      "name": "Lan Huang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Nan Zhang"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Siyu Tang"
    },
    {
      "affs": [
        6
      ],
      "name": "Samina Ejaz Syed",
      "orcid": "0000-0002-0800-6808"
    },
    {
      "affs": [
        0
      ],
      "name": "Shufang Liang",
      "orcid": "0000-0003-1000-7508"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8fm1gxetd4s31.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78603",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731071/",
  "id": "8fm1gxetd4s31",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78603",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "2713|Hepatitis B Virus Studies"
    ]
  ],
  "openalex": "W7225176440",
  "pdf_url": null,
  "pmcid": "PMC13731071",
  "pmid": "42977576",
  "published": "2026-11-03",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/8fm1gxetd4s31.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:20Z",
      "native_id": "PMC13731071",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78603"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Hepatitis B Virus Studies",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "SUMOylated DDX3 Promotes HBV Replication and Tumor Growth of Hepatocellular Carcinoma via TRIM28‐DDX3‐KLF4α Signaling Axis",
  "title_text": "SUMOylated DDX3 Promotes HBV Replication and Tumor Growth of Hepatocellular Carcinoma via TRIM28‐DDX3‐KLF4α Signaling Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:20Z",
  "url": "https://research.draconitic.com/paper/8fm1gxetd4s31",
  "venue": "Advanced Science",
  "versions": []
}