{
  "abstract": "N-Nitrosodimethylamine (NDMA) is a potent carcinogen implicated in hepatocellular carcinoma (HCC) pathogenesis and cancer stem cell (CSC) emergence. Zinc finger protein ZNF652 exhibits tumor-suppressive properties, while Sonic Hedgehog signaling promotes CSC characteristics. Sulforaphane (SFN), a natural compound, shows anticancer potential, but its regulatory role in NDMA-induced liver CSCs remains unclear. This study aimed to investigate the ZNF652/Sonic Hedgehog axis in NDMA-induced liver CSCs and elucidate SFN's inhibitory effects through this pathway. An in vitro NDMA-induced HCC cell model and in vivo xenograft experiments were combined with molecular analyses to explore mechanisms. Bioinformatics analyses evaluated ZNF652's prognostic significance and Sonic Hedgehog pathway correlation. In vitro experiments induced LO2 cell malignant transformation via chronic NDMA exposure, performed sphere formation assays, and validated ZNF652/GLI1 interactions through overexpression, downregulation, and dual-luciferase assays. In vivo subcutaneous xenograft models treated with SFN (12.5/25 mg/kg) demonstrated dose-dependent tumor suppression, reduced CD133/GLI1 expression, and restored ZNF652 levels. Chronic NDMA exposure (1 μg/mL) transformed LO2 hepatocytes into malignant TLO2 cells with CSC traits, including elevated HCC, CSC and EMT markers. ZNF652 expression decreased in metastatic HCC tissues and NDMA-induced CSCs. Overexpressing ZNF652 reduced sphere formation, suppressed CSC markers (CD133, SOX2, OCT4, EPCAM), and inhibited Sonic Hedgehog pathway activity by directly targeting GLI1 via promoter binding. SFN treatment diminished CSC self-renewal, downregulated GLI1 expression, and reversed ZNF652 knockdown-induced CSC properties in vitro. In nude mouse xenografts, SFN dose-dependently reduced tumor volume/weight, lowered CD133/GLI1 levels, and restored ZNF652 expression compared to NDMA-exposed group. SFN inhibits NDMA-induced liver cancer stemness via the ZNF652/Sonic Hedgehog axis, offering a novel therapeutic strategy for hepatocellular carcinoma.",
  "abstract_shown": true,
  "affiliations": [
    "Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Wenzhou Meidical University, Ningbo, Zhejiang, China.",
    "Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China.",
    "Department of Clinical Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.",
    "Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.",
    "Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.",
    "Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jinyi Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoqian Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongxue Ren"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongcheng Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Liping He"
    },
    {
      "affs": [
        3
      ],
      "name": "Yue Chen"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Caiyun Zhong"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoting Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Hongyu Han"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8rdjw6y3zvy04.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1965529",
  "fulltext_url": "https://europepmc.org/articles/PMC13713818",
  "id": "8rdjw6y3zvy04",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953186",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Cells and Metastasis"
    ]
  ],
  "openalex": "W7221766766",
  "pdf_url": "https://europepmc.org/articles/PMC13713818?pdf=render",
  "pmcid": "PMC13713818",
  "pmid": "42953186",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8rdjw6y3zvy04.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953186",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953186"
    },
    {
      "first_seen": "2026-11-01T12:21:25Z",
      "native_id": "PMC13713818",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1965529"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "Sulforaphane inhibits N-nitrosodimethylamine induced hepatocellular carcinoma stem cell properties via ZNF652/Sonic hedgehog axis.",
  "title_text": "Sulforaphane inhibits N-nitrosodimethylamine induced hepatocellular carcinoma stem cell properties via ZNF652/Sonic hedgehog axis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:25Z",
  "url": "https://research.draconitic.com/paper/8rdjw6y3zvy04",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}