Alpha-fetoprotein (AFP) is a well-established biomarker for hepatocellular carcinoma (HCC). Here, we investigated the acetylation state of AFP in vivo. AFP acetylation was regulated by the acetyltransferase CBP and the deacetylase SIRT1. Acetylation of AFP at lysines 194, 211, and 242 increased the stability of AFP protein by decreasing its ubiquitination and proteasomal degradation. AFP acetylation promoted its oncogenic role by blocking binding to the phosphatase PTEN and the pro-apoptotic protein caspase-3, which increased signaling for proliferation, migration, and invasion and decreased apoptosis. High levels of acetylated AFP in HCC tissues were associated with HBV infection and correlated with poor prognosis and decreased patient survival. In HCC cells, hepatitis B virus X protein (HBx) and palmitic acid (PA) increased the level of acetylated AFP by disrupting SIRT1-mediated deacetylation. AFP acetylation plays an important role in HCC progression and provides a new potential prognostic marker and therapeutic target for HCC.

中文翻译：

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甲胎蛋白的乙酰化促进肝细胞癌的进展。

甲胎蛋白（AFP）是肝细胞癌（HCC）公认的生物标志物。在这里，我们调查了体内AFP的乙酰化状态。AFP乙酰化受乙酰基转移酶CBP和脱乙酰基酶SIRT1调控。AFP在赖氨酸194、211和242上的乙酰化可通过减少AFP蛋白的泛素化和蛋白酶体降解来提高其稳定性。AFP乙酰化通过阻断与磷酸酶PTEN和促凋亡蛋白caspase-3的结合来促进其致癌作用，这增加了增殖，迁移和侵袭的信号传导并减少了细胞凋亡。肝癌组织中高水平的乙酰化AFP与HBV感染有关，并与不良预后和患者生存率降低相关。在肝癌细胞中 乙型肝炎病毒X蛋白（HBx）和棕榈酸（PA）通过破坏SIRT1介导的脱乙酰基作用提高了乙酰化AFP的水平。AFP乙酰化在HCC进展中起重要作用，并为HCC提供了新的潜在预后标志物和治疗靶标。