中国肿瘤生物治疗杂志2026，Vol.33Issue(1)：66-76,11.DOI:10.3872/j.issn.1007-385x.2026.01.009
IGF2BP3和UXS1在肝细胞癌中的表达、靶向调控及协同作用机制
Expression characteristics,targeted regulation,and synergistic mechanisms of IGF2BP3 and UXS1 in hepatocellular carcinoma
摘要
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.关键词
肝细胞癌/胰岛素样生长因子2 mRNA结合蛋白3/尿苷二磷酸-葡萄糖醛酸脱羧酶1/糖代谢重编程/单细胞测序/巨噬细胞迁移抑制因子通路分类
医药卫生引用本文复制引用
邓玉龙,韦莲青,吴星辰,谢晓婷,熊丹丹..IGF2BP3和UXS1在肝细胞癌中的表达、靶向调控及协同作用机制[J].中国肿瘤生物治疗杂志,2026,33(1):66-76,11.基金项目
广西自然科学基金(2024GXNSFAA010057) （2024GXNSFAA010057）
国家级大学生创新创业训练计划项目(202410598035) （202410598035）
广西医科大学未来学术之星基金(WLXSZX24076) （WLXSZX24076）
