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<p>Hepatocellular carcinoma (HCC) is a highly prevalent malignancy with persistently high and increasing mortality rates. Once regarded merely as a metabolic byproduct, lactate is now recognized as a key metabolite in the tumor microenvironment (TME), where it promotes HCC progression through diverse biological functions. Lactylation, a unique post-translational modification, regulates the TME by altering gene expression via the addition of lactate-derived groups to both histone and non-histone proteins. This review summarizes the role of lactate metabolism in the body, examines its effects on various immune cell populations, and highlights recent advances in anti-HCC therapies targeting lactate.</p>

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Lactate and lactylation in hepatocellular carcinoma: A new frontier in metabolic–epigenetic interactions

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Chen Chen,
  • Yangyang Miao,
  • Songsong Fan,
  • Chengji Tang,
  • Rui Peng,
  • Jiahao Zhang,
  • Jun Cao,
  • Chi Zhang,
  • Dousheng Bai

摘要

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy with persistently high and increasing mortality rates. Once regarded merely as a metabolic byproduct, lactate is now recognized as a key metabolite in the tumor microenvironment (TME), where it promotes HCC progression through diverse biological functions. Lactylation, a unique post-translational modification, regulates the TME by altering gene expression via the addition of lactate-derived groups to both histone and non-histone proteins. This review summarizes the role of lactate metabolism in the body, examines its effects on various immune cell populations, and highlights recent advances in anti-HCC therapies targeting lactate.