肝细胞癌（HCC）是肝部癌症最常见的类型，在非洲和亚洲地区有较高的患病率。SYVN1在HCC中上调表达，但SYVN1在免疫逃避中的生物学作用仍不清楚。使用RT-qPCR和Western blot检测HCC细胞和组织中SYVN1和关键分子的表达水平。流式细胞术用于确定T细胞的比例，酶联免疫吸附实验用于确定分泌的IFN-γ的数量。使用CCK-8和集落形成实验监测细胞存活率。使用转移试验检测HCC细胞的转移特性。使用生物信息学分析、ChIP和荧光素酶实验研究PD-L1的转录调控。使用共免疫沉淀检测SYVN1和FoxO1之间的直接相互作用以及FoxO1的泛素化。在异种移植和肺转移模型中验证了体外研究发现。在HCC细胞和组织中，SYVN1上调而FoxO1下调。SYVN1敲除或FoxO1过度表达降低了PD-L1的表达，并抑制了HCC细胞的免疫逃避、细胞生长和转移。机制上，FoxO1以β-联蛋白依赖或独立方式调控PD-L1转录。功能研究进一步表明，SYVN1通过促进FoxO1的泛素蛋白酶依赖性降解来促进免疫逃避、细胞增殖、迁移和侵袭。体内研究表明，静默SYVN1抑制了HCC细胞的免疫逃避和转移，可能是通过FoxO1 / PD-L1轴实现的。SYVN1通过调节FoxO1的泛素化刺激β-联蛋白核转位，从而促进HCC中PD-L1介导的转移和免疫逃避。©2023年作者。

A high incidence of hepatocellular carcinoma (HCC), the most frequently diagnosed form of liver cancer, is observed in Africa and Asia. SYVN1 is upregulated in HCC; however, the biological roles of SYVN1 in immune evasion remain unclear.RT-qPCR and western blot were employed to detect the expression levels of SYVN1 and the key molecules in HCC cells and tissues. Flow cytometry was used to determine the proportion of T cells, and an ELISA assay was used to determine the amount of IFN-γ secreted. Cell viability was monitored by CCK-8 and colony formation assays. The metastatic properties of HCC cells were detected by Transwell assays. Bioinformatics analysis, ChIP, and luciferase assays were used to study the transcriptional regulation of PD-L1. Co-IP was used to detect direct interaction between SYVN1 and FoxO1, as well as the ubiquitination of FoxO1. The in vitro findings were validated in xenograft and lung metastasis models.In HCC cells and tissues, SYVN1 was upregulated while FoxO1 was downregulated. SYVN1 knockdown or FoxO1 overexpression reduced PD-L1 expression, and inhibited immune evasion, cell growth, and metastasis in HCC cells. Mechanistically, FoxO1 regulated PD-L1 transcription in a β-catenin-independent or -dependent manner. Functional studies further showed that SYVN1 promoted immune evasion, cell proliferation, migration and invasion via facilitating ubiquitin-proteasome-dependent degradation of FoxO1. In vivo investigations showed that silencing of SYVN1 inhibited immune evasion and metastasis of HCC cells, possible via the FoxO1/PD-L1 axis.SYVN1 regulates FoxO1 ubiquitination to stimulate β-catenin nuclear translocation and promotes PD-L1-mediated metastasis and immune evasion in HCC.© 2023. The Author(s).