Guo Jingheng, Cheng Qian, Li Yongjian, Tian Lingyu, Ma Delin, Li Zhao, Gao Jie, Zhu Jiye
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China.
Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People's Hospital, Beijing, China.
Clin Med Insights Oncol. 2023 Jul 4;17:11795549231181189. doi: 10.1177/11795549231181189. eCollection 2023.
The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing globally, and its prognosis has not improved substantially in recent years. Understanding the pathogenesis of ICC may provide a theoretical basis for its treatment. In this study, we investigated the effects and underlying mechanisms of fucosyltransferase 5 (FUT5) on the malignant progression of ICC.
FUT5 expression in ICC samples and adjacent nontumor tissues was compared using quantitative real-time polymerase chain reaction and immunohistochemical assays. We performed cell counting kit-8, colony formation, and migration assays to determine whether FUT5 influenced the proliferation and mobility of ICC cells. Finally, mass spectrometry was performed to identify the glycoproteins regulated by FUT5.
FUT5 mRNA was significantly upregulated in most ICC samples compared with corresponding adjacent nontumor tissues. The ectopic expression of FUT5 promoted the proliferation and migration of ICC cells, whereas FUT5 knockdown significantly suppressed these cellular properties. Mechanistically, we demonstrated that FUT5 is essential for the synthesis and glycosylation of several proteins, including versican, β3 integrin, and cystatin 7, which may serve key roles in the precancer effects of FUT5.
FUT5 is upregulated in ICC and promotes ICC development by promoting glycosylation of several proteins. Therefore, FUT5 may serve as a therapeutic target for the treatment of ICC.
肝内胆管癌（ICC）的发病率在全球范围内呈上升趋势，且近年来其预后并未得到显著改善。了解ICC的发病机制可能为其治疗提供理论依据。在本研究中，我们调查了岩藻糖基转移酶5（FUT5）对ICC恶性进展的影响及其潜在机制。
使用定量实时聚合酶链反应和免疫组织化学分析比较ICC样本和相邻非肿瘤组织中FUT5的表达。我们进行了细胞计数试剂盒-8、集落形成和迁移试验，以确定FUT5是否影响ICC细胞的增殖和迁移能力。最后，进行质谱分析以鉴定受FUT5调节的糖蛋白。
与相应的相邻非肿瘤组织相比，大多数ICC样本中FUT5 mRNA显著上调。FUT5的异位表达促进了ICC细胞的增殖和迁移，而FUT5基因敲低则显著抑制了这些细胞特性。机制上，我们证明FUT5对包括多功能蛋白聚糖、β3整合素和半胱氨酸蛋白酶抑制剂7在内的几种蛋白质的合成和糖基化至关重要，这些蛋白质可能在FUT5的癌前效应中起关键作用。
FUT5在ICC中上调，并通过促进几种蛋白质的糖基化来促进ICC的发展。因此，FUT5可能成为治疗ICC的一个治疗靶点。
