{
  "abstract": "Background The liver possesses a remarkable regenerative capacity, which facilitates rapid recovery from various forms of injury. While hepatocyte proliferation is central to this regenerative process, the underlying regulatory mechanisms that drive hepatocyte renewal following partial hepatectomy remain incompletely understood. The histone demethylase JMJD2D plays a well-established role in promoting cancer cell proliferation. However, its specific function and molecular mechanisms in the context of physiological liver regeneration and hepatocyte proliferation remain poorly understood.Methods To investigate the role and molecular mechanism of JMJD2D in liver regeneration, we generated JMJD2D knockout (JMJD2D -/-) mice and subjected them to 70% partial hepatectomy. JMJD2D knockdown was also performed using shRNA-mediated silencing to examine its effect on hepatocyte proliferation. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays were employed to explore the functional interaction between JMJD2D and YAP, and to assess its regulatory role in FOXM1 transcription and downstream proliferation-related gene expression during liver regeneration and cancer progression.Results JMJD2D deficiency markedly impaired liver regeneration after two-thirds partial hepatectomy and suppressed liver cancer growth, accompanied by reduced expression of FOXM1 and its downstream proliferation-related genes. In hepatocellular carcinoma cells, JMJD2D knockdown similarly diminished FOXM1 levels and the expression of its target genes. Consistently, JMJD2D and FOXM1 expression showed a positive correlation in clinical liver cancer specimens. Mechanistically, JMJD2D interacts with YAP to enhance FOXM1 transcription and activate a proliferative gene program, thereby promoting both liver regeneration and liver cancer progression ( IDDF2026-ABS-0293 Figure 1. JMJD2D cooperates with YAP to promote the expression of the regenerative regulatory factor FOXM1 and proliferation-related genes, thereby facilitating liver regeneration).Conclusions JMJD2D cooperates with YAP to promote the expression of the regenerative regulatory factor FOXM1 and proliferation-related genes, thereby facilitating liver regeneration and the proliferation of liver cancer.Abstract IDDF2026-ABS-0293 Figure 1",
  "authors": [
    {
      "affiliations": [
        "School of Medicine, Xiamen University, China"
      ],
      "name": "Rubing Liang"
    },
    {
      "affiliations": [
        "School of Medicine, Xiamen University, China"
      ],
      "name": "Xu Kong"
    },
    {
      "affiliations": [
        "Xiang’an Hospital of Xiamen University, China"
      ],
      "name": "Wengang Li"
    }
  ],
  "title": "IDDF2026-ABS-0293 JMJD2D is required for YAP-mediated liver regeneration and hepatocellular carcinoma progression",
  "uid": "4cff10de-4f5a-57c2-b053-a3b32965366d"
}