{
  "abstract": "Background Hepatocellular carcinoma (HCC) is a highly aggressive tumor with a poor prognosis, necessitating the exploration of its pathogenic mechanisms and novel therapeutic targets. SLC26A6, an anion exchanger, is expressed at low levels in normal liver but shows elevated expression in HCC tissues according to TCGA data, suggesting its potential involvement in HCC. This study aims to investigate the role of SLC26A6 in hepatocarcinogenesis.Methods Hepatic-specific SLC26A6-overexpressing (OE) mice were generated on a C57BL/6 background. Overexpression of SLC26A6 was also established in normal human hepatocyte lines (MIHA and HepLi5). HCC models were induced in mice using DEN/CCl4, DEN combined with a high-fat high-cholesterol diet (HFHCD), or DEN alone.Results In all murine HCC models, SLC26A6-OE mice exhibited significantly higher HCC incidence and developed more and larger liver tumors compared to wild-type (WT) mice. Notably, under HFHCD conditions, HCC developed only in SLC26A6-OE mice after 48 weeks. Under normal diet and spontaneous aging, SLC26A6-OE mice displayed mild steatosis at 6 months, steatohepatitis at 12 months, and 33.33% developed HCC by 24 months, while WT mice remained pathology-free. These findings confirm that SLC26A6 promotes carcinogen-induced, diet-induced, and spontaneous hepatocarcinogenesis. In vitro, SLC26A6 overexpression in MIHA and HepLi5 cells enhanced intracellular lipid accumulation. Mechanistically, SLC26A6 upregulated lipid metabolism regulators (SREBP1, SREBP2, PPARα, PPARγ) and their downstream targets (e.g., CD36, FASN, HMGCR), along with oncogenic transcription factors c-FOS and c-JUN in both murine models and hepatic cell lines.Conclusions SLC26A6 promotes HCC carcinogenesis and progression by modulating lipid metabolism and activating FOS/JUN signaling.",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China"
      ],
      "name": "Xin Li"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China"
      ],
      "name": "Jiajia Li"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China"
      ],
      "name": "Qian Liu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China"
      ],
      "name": "Xuemei Liu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China"
      ],
      "name": "Biguang Tuo"
    }
  ],
  "title": "IDDF2026-ABS-0188 SLC26A6 promotes the carcinogenesis and growth of hepatocellular carcinoma through modulating lipid metabolism and FOS/JUN signaling",
  "uid": "87cc39c3-35a9-5a5c-a620-e43993786424"
}