Wang Pengfei, Liu Xuxu, Yu Jingjing, Meng Ziang, Lv Zhenyi, Shang Ce, Geng Qi, Wang Dawei, Xue Dongbo, Li Long
Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
J Inflamm Res. 2023 Feb 21;16:747-768. doi: 10.2147/JIR.S396484. eCollection 2023.
Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated mortality worldwide. Fucosyltransferases (FUTs) are associated with numerous cancers. We aimed to investigate the functions of FUTs in COAD.
Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the expression and clinical relevance of FUTs in COAD. Real Time Quantitative PCR (RT-qPCR), Western blot, immunohistochemistry and ELISA were used to detect the relative RNA and protein expression levels. Colitis-associated cancer mice treated with Fusobacterium nucleatum were used to illustrate the effects of Fusobacterium nucleatum on FUTs and COAD. Luciferase reporting assay was used to investigate the binding of miRNA to mRNA.
TCGA and GEO datasets showed abnormal expression of FUTs in COAD at transcript level. RT-qPCR, Western blot and immunohistochemistry showed increased expression of FUT1, POFUT1 and POFUT2 in COAD. COAD patients with a high expression of FUT1, FUT11, FUT13 (POFUT2) had a worse prognosis, while patients with a high expression of FUT2, FUT3, FUT6 had a better prognosis. FUT1 and POFUT2 could independently predict the prognosis of COAD patients. Functional analysis by CancerSEA database showed that FUT3, FUT6, FUT8, FUT12 (POFUT1) and FUT13 are associated with differentiation, apoptosis, invasion, quiescence, and hypoxia. FUTs are associated with the tumor microenvironment of COAD. FUT1 regulated by miR-939-3p inhibit the expression of MUC2. Fusobacterium nucleatum may affect the expression of FUTs by affecting their transcription factors and miRNA levels. Moreover, Fusobacterium nucleatum promotes COAD progression through the miR-939-3p/FUT1/MUC2 axis.
Fucosyltransferases play an important role and may be the mediator of Fusobacterium nucleatum promoting COAD progression.
结肠腺癌（COAD）是全球癌症相关死亡的主要原因之一。岩藻糖基转移酶（FUTs）与多种癌症相关。我们旨在研究FUTs在COAD中的作用。
使用来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的转录组和临床数据，分析FUTs在COAD中的表达及临床相关性。采用实时定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法、免疫组织化学和酶联免疫吸附测定（ELISA）检测相对RNA和蛋白质表达水平。使用经具核梭杆菌处理的结肠炎相关癌小鼠，以阐明具核梭杆菌对FUTs和COAD的影响。采用荧光素酶报告基因检测法研究微小RNA（miRNA）与信使核糖核酸（mRNA）的结合情况。
TCGA和GEO数据集显示，在转录水平上，COAD中FUTs表达异常。RT-qPCR、蛋白质免疫印迹法和免疫组织化学显示，COAD中FUT1、POFUT1和POFUT2表达增加。FUT1、FUT11、FUT13（POFUT2）高表达的COAD患者预后较差，而FUT2、FUT3、FUT6高表达的患者预后较好。FUT1和POFUT2可独立预测COAD患者的预后。通过CancerSEA数据库进行的功能分析表明，FUT3、FUT6、FUT8、FUT12（POFUT1）和FUT13与分化、凋亡、侵袭、静止和缺氧相关。FUTs与COAD的肿瘤微环境相关。由miR-939-3p调控的FUT1抑制黏蛋白2（MUC2）的表达。具核梭杆菌可能通过影响其转录因子和miRNA水平来影响FUTs的表达。此外，具核梭杆菌通过miR-939-3p/FUT1/MUC2轴促进COAD进展。
岩藻糖基转移酶发挥重要作用，可能是具核梭杆菌促进COAD进展的介质。
