Chu Xuan, Zhang Ligai, Xiang Shiqing, Huang Yuting
Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, P. R. China.
Sci Rep. 2025 Jul 24;15(1):26901. doi: 10.1038/s41598-025-12619-x.
UDP-glucose: glycoprotein glucosyltransferase 1 (UGGT1), a key component of the endoplasmic reticulum quality control (ERQC) system, has established roles in metabolic/infectious diseases, but its oncogenic potential remains unclear. UGGT1's expression, genetic alterations, methylation patterns, immune function and interacting genes were evaluated through different bioinformatics databases, and the roles of UGGT1 in breast cancer were validated by in vitro experiments. UGGT1 was significantly overexpressed in most cancers, correlating with advanced stage and poor survival. Variations in its promoter methylation and mutation patterns across cancers were associated with patient outcomes. UGGT1 status (expression/mutation) was significantly associated with immune cell infiltration in the tumor microenvironment. Functional enrichment linked UGGT1 co-expressed genes to cell cycle and nucleic acid metabolism. Critically, UGGT1 knockdown inhibited breast cancer cell proliferation/migration in vitro and downregulated key ER stress sensors (IRE1α, ATF6, PERK). This study establishes UGGT1 as a significant pan-cancer prognostic biomarker and reveals its role in tumor progression, highlighting its potential as a therapeutic target.
糖蛋白葡糖基转移酶1（UGGT1）是内质网质量控制系统（ERQC）的关键组成部分，在代谢/感染性疾病中已明确其作用，但其致癌潜力仍不清楚。通过不同的生物信息学数据库评估了UGGT1的表达、基因改变、甲基化模式、免疫功能和相互作用基因，并通过体外实验验证了UGGT1在乳腺癌中的作用。UGGT1在大多数癌症中显著过表达，与晚期和不良生存相关。其启动子甲基化和跨癌症的突变模式变化与患者预后相关。UGGT1状态（表达/突变）与肿瘤微环境中的免疫细胞浸润显著相关。功能富集将UGGT1共表达基因与细胞周期和核酸代谢联系起来。至关重要的是，UGGT1敲低在体外抑制乳腺癌细胞增殖/迁移，并下调关键的内质网应激传感器（IRE1α、ATF6、PERK）。本研究将UGGT1确立为一种重要的泛癌预后生物标志物，并揭示了其在肿瘤进展中的作用，突出了其作为治疗靶点的潜力。
