[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC） 中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库 的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNAseq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织 中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增 殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调， 后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞 的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432， P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量 代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、 UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1 在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

[Abstract] Objective: To investigate the expression characteristics and prognostic significance of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and the uridine diphosphate-glucuronate decarboxylase 1 (UXS1) as well as the molecular mechanisms of the synergistic interaction between them in hepatocellular carcinoma (HCC). Methods: Transcriptomic data from multiple public databases, including UALCAN, cBioPortal, ENCORI, TISCH2, and GDSC were integrated to analyze the expressions, prognosis, functional enrichment, and drug sensitivity of IGF2BP3 and UXS1. Single-cell RNA sequencing (scRNA-seq) data from the GEO repository were further collected to examine cell-cell communication and single-cell metabolic activity, thereby systematically analyzing the specific function of the IGF2BP3- UXS1 axis in HCC. Results: The expressions of IGF2BP3 and UXS1 were significantly upregulated in HCC tissues, and high expressions of either gene were associated with markedly shorter overall survival (both P < 0.05). CRISPR-mediated knockout of IGF2BP3 or UXS1 substantially suppressed the proliferative capacity of multiple HCC cell lines. scRNA-seq analysis revealed broad expressions of both genes across hepatic cell population: IGF2BP3 expression was upregulated during late-stage hepatocyte differentiation, whereas UXS1 was highly expressed during early and mid differentiation stages. High expressions of IGF2BP3 or UXS1 significantly activated the MIF signaling pathway. Elevated expression of IGF2BP3 weakened the interactions between fibroblast-tumor cells, while high expression of UXS1 enhanced T-cell signal transduction. A significant positive correlation was observed between the expressions of IGF2BP3 and UXS1 (r = 0.432, P < 0.05). Silencing of the IGF2BP3 binding site resulted in changes in UXS1 expression levels (F = 0.333). Functional enrichment analyses indicated that IGF2BP3 and UXS1 synergistically regulated key biological processes, including energy metabolism and protein translation. Moreover, both genes showed strong associations with multiple glycometabolic pathways in high-expression tumor subpopulations. Patients with high IGF2BP3 or UXS1 expressions exhibited heightened sensitivity to uprosertib and pronounced resistance to navitoclax. Conclusion: IGF2BP3 and UXS1 are highly expressed in HCC. Both genes promote malignant biological behaviors of HCC by regulating coordinated reprogramming of glucose metabolism.

[基金项目] 广西自然科学基金（2024GXNSFAA010057）；国家级大学生创新创业训练计划项目（202410598035）；广西医科大 学未来学术之星基金（WLXSZX24076）