GALNT4介导的TYRO3糖基化对子宫内膜癌的恶性生物学行为的影响  

Impact of TYRO3 glycosylation mediated by GalNAc transferase 4 on the malignant biological behavior of endometrial carcinoma

作　　者：朱一麟[1] 高雪梅[1] 孟红娟[1] 刘艳 Zhu Yilin;Gao Xuemei;Meng Hongjuan;Liu Yan(Department of Obstetrics and Gynecology,Wuhan Hospital of Integrated Traditional Chinese and Western Medicine)

机构地区：[1]武汉市中西医结合医院妇产科,武汉430022

出　　处：《重庆医科大学学报》2025年第2期217-223,共7页Journal of Chongqing Medical University

基　　金：湖北省自然科学基金青年资助项目(编号:2022CFB991)。

摘　　要：目的:探讨多肽GalNAc转移酶4(GalNAc transferases,GALNT4)通过介导蛋白酪氨酸激酶受体(protein tyrosine kinase receptor,TYRO3)糖基化影响子宫内膜癌(endometrial carcinoma,ECa)的恶性生物学行为的分子机制。方法:研究人群包括从106例ECa患者中收集的福尔马林固定石蜡包埋的ECa组织样本制作组织微阵列。分析GALNT4表达与患者诊断时的年龄、疾病阶段、淋巴血管侵犯、生存结局的关系。人ECa细胞系Ishikawa和RL95-2转染GALNT4-特异性siRNA或GALNT4质粒以敲低或上调GALNT4表达。采用si-TYRO3处理GALNT4过表达的Ishikawa细胞。通过Transwell实验测量了细胞的迁移、侵袭能力。将GALNT4过表达或敲低的Ishikawa细胞注射到NOD/SCID小鼠脾脏中以诱导肝转移,分析肝转移病灶数量。结果:ECa组织中GALNT4的表达较正常组织增加(P<0.05)。GALNT4低表达组和GALNT4高表达组在年龄、组织学类型、国际妇产联盟(International Federation of Gynecology and Obstetrics,FIGO)分期存在差异(P<0.05)。GALNT4表达水平与OS呈负相关,HR为2.610(95%CI=1.094~6.226)(P<0.05)。GALNT4高表达组的总生存期低于GALNT4低表达组(P<0.05)。与Vector组相比,GALNT4组Ishikawa和RL95-2细胞迁移和侵袭细胞数增加(P<0.05)。与si-NC组相比,si-GALNT4#1、si-GALNT4#2组Ishikawa和RL95-2细胞的迁移、侵袭细胞数降低(P<0.05)。与Vector组相比,GALNT4组Ishikawa细胞肝转移病灶数量增加(P<0.05)。相反,与si-NC组相比,si-GALNT4#1、si-GALNT4#2组Ishikawa细胞肝转移病灶数量减少(P<0.05)。与GALNT4+si-NC组相比,GALNT4+si-TYRO3组Ishikawa细胞的迁移、侵袭细胞数降低(P<0.05)。结论:GALNT4在ECa组织中过表达,并与不良预后相关。机制研究显示,GALNT4促进ECa细胞迁移、侵袭的行为部分是通过修饰TYRO3的O-糖基化和蛋白稳定性实现。Objective:To investigate the molecular mechanism of action of the polypeptide GalNAc transferase 4(GALNT4)on the malignant biological behavior of endometrial carcinoma(ECa)by mediating the glycosylation of receptor tyrosine kinase TYRO3.Methods:Formalin-fixed paraffin-embedded ECa tissue samples were collected from 106 ECa patients to prepare tissue microarrays.The association of the expression of GALNT4 with the age at diagnosis,disease stage,lymphovascular invasion,and survival outcome was analyzed.Human ECa cell lines Ishikawa and RL95-2 were transfected with GALNT4-specific siRNA or GALNT4 plasmid to knockdown or upregulate the expression of GALNT4,and Ishikawa cells with GALNT4 overexpression were treated with si-TYRO3.Transwell assay was used to assess the migration and invasion abilities of cells.Ishikawa cells with GALNT4 overexpression or knockdown were injected into the spleen of NOD/SCID mice to induce liver metastasis,and the number of liver metastatic lesions was analyzed.Results:The expression level of GALNT4 in ECa tissue was significantly higher than that in normal tissue(P<0.05).There were significant differences in age,histological type,and FIGO stage between the low-expression GALNT4 group and the high-expression GALNT4 group(P<0.05).The expression level of GALNT4 was negatively correlated with overall survival(hazard ratio=2.610,95%CI=1.094-6.226,P<0.05).The high-expression GALNT4 group had a significantly shorter overall survival time than the low-expression GALNT4 group(P<0.05).Compared with the Vector group,the GALNT4 group had significant increases in the migration and invasion of Ishikawa and RL95-2 cells(P<0.05).Compared with the si-NC group,the si-GALNT4#1 and si-GALNT4#2 groups had significant reductions in the migration and invasion of Ishikawa and RL95-2 cells(P<0.05).Compared with the Vector group,the GALNT4 group had a significant increase in the number of liver metastatic lesions due to Ishikawa cells(P<0.05),and on the contrary,compared with the si-NC group,the si-GALNT4#1 and si

关 键 词：多肽GalNAc转移酶4 蛋白酪氨酸激酶 子宫内膜癌 糖基化 

分 类 号：R737.33[医药卫生—肿瘤]