{
  "abstract": "Hepatocellular carcinoma (HCC) exhibits a high propensity for metastasis and recurrence, leading to poor prognosis. Intrahepatic metastasis is more common than extrahepatic spread. Metastases arise through diverse mechanisms, including the involvement of cancer stem cells (CSCs) and the immune-modulatory role of the liver tissue microenvironment. As hepatic resident macrophages, Kupffer cells play a critical role in immune surveillance by phagocytosing disseminated HCC cells. However, the molecules regulating HCC cell stemness properties, Kupffer cell phagocytosis, and further HCC intrahepatic metastasis remain poorly understood. In the present study, we found that the long noncoding RNA LINC02709 was upregulated in HCC and correlated with stemness properties, intrahepatic metastasis, and poor prognosis. LINC02709 not only enhanced stemness properties of HCC cells, but also suppressed the phagocytosis of HCC cells by Kupffer cells, leading to increased liver metastasis. LINC02709 upregulated CD24 and CD47, which mediated the effects of LINC02709 on HCC cell stemness properties and Kupffer cell phagocytosis. LINC02709 was identified as an m6A-modified transcript. m6A-modified LINC02709 bound and recruited the m6A reader FXR1 and the DNA demethylase TET1 to the CD24 and CD47 promoters, inducing DNA demethylation and transcriptional activation of CD24 and CD47. The effects of LINC02709 on CD24/CD47, stemness properties, phagocytosis, and liver metastasis were all dependent on m6A modification. Our findings demonstrate that m6A-modified LINC02709 is a novel and promising biomarker for HCC recurrence and survival, enhancing HCC cell stemness properties, suppressing Kupffer cell phagocytosis, and driving HCC intrahepatic metastasis by epigenetically activating CD24 and CD47. Targeting m6A-modified LINC02709 represents a promising therapeutic strategy for HCC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China",
    "Guangxi Clinical Medical Research Center of Hepatobiliary Disease, Baise, China",
    "Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China",
    "Graduate College of Youjiang Medical University for Nationalities, Baise, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Huamei Wei",
      "orcid": "0000-0003-4271-0847"
    },
    {
      "affs": [
        2
      ],
      "name": "Wenchuan Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Xianjian Wu"
    },
    {
      "affs": [
        3
      ],
      "name": "Rongzhou Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Gaoxiong Tan"
    },
    {
      "affs": [
        3
      ],
      "name": "Yunyu Wei"
    },
    {
      "affs": [
        2
      ],
      "name": "Quan Fang"
    },
    {
      "affs": [
        3
      ],
      "name": "Youguan Huang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Zhongheng Wei",
      "orcid": "0009-0005-5372-2693"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jian Pu",
      "orcid": "0000-0001-5071-4595"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/asva8rcpdbzqd.bib",
  "cited_by": 0,
  "doi": "10.1038/s41420-026-03276-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13748585/",
  "id": "asva8rcpdbzqd",
  "issns": [
    "2058-7716"
  ],
  "landing_url": "https://doi.org/10.1038/s41420-026-03276-8",
  "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",
      "Article"
    ],
    [
      "openalex",
      "1306|Cancer-related molecular mechanisms research"
    ]
  ],
  "openalex": "W7202267887",
  "pdf_url": "https://www.nature.com/articles/s41420-026-03276-8_reference.pdf",
  "pmcid": "PMC13748585",
  "pmid": "43003835",
  "published": "2026-08-12",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/asva8rcpdbzqd.ris",
  "sources": [
    {
      "first_seen": "2026-11-13T12:26:33Z",
      "native_id": "PMC13748585",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41420-026-03276-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer-related molecular mechanisms research",
      "subfield": "oncology"
    }
  ],
  "title": "LINC02709 facilitates hepatocellular carcinoma metastasis by increasing stem cell-like properties and suppressing Kupffer cell phagocytosis",
  "title_text": "LINC02709 facilitates hepatocellular carcinoma metastasis by increasing stem cell-like properties and suppressing Kupffer cell phagocytosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:26:33Z",
  "url": "https://research.draconitic.com/paper/asva8rcpdbzqd",
  "venue": "Cell Death Discovery",
  "versions": []
}