江苏大学学报（医学版）2025，Vol.35Issue(2)：102-109,117,9.DOI:10.13312/j.issn.1671-7783.y240159
O-GlcNAc糖基化修饰对胃癌细胞黏附能力的影响
Effects of O-GlcNAcylation on the adhesion ability of gastric cancer cells
摘要
Abstract
Objective:To investigate the effect of O-linked N-acetylglucosamine(O-GlcNAc)glycosylation on the adhesion between gastric cancer cells and extracellular matrix and its potential mechanisms.Methods:The mRNA expressions of glutamine-fructose-6-phosphate transaminase 1(GFPT1),glucosamine-phosphate N-acetyltransferase 1(GNPNAT1),phosphoglucomutase 3(PGM3),UDP-N-acetylglucosamine pyrophosphorylase 1(UAP1),N-acetylglucosamine transferase(OGT)and O-GlcNAcase(OGA)in pan-cancer and human gastric cancer tissues were analyzed by UALCAN database.The relative mRNA expression levels of GFPT1,GNPNAT1,PGM3,UAP1,OGT and OGA in gastric cancer HGC-27,AGS,and SNU-1 cells were analyzed by DepMap database.The relative expression levels of GFPT1,OGT and OGA proteins and the glycosylation modification levels of O-GlcNAc in human gastric mucosal epithelial GES-1 cells and gastric cancer HGC-27,AGS and SNU-1 cells were detected by Western blotting.The signaling pathways enriched by the gastric cancer samples with differential expression of OGT and OGA were explored by Gene Set Enrichment Analysis(GSEA).The adhesion ability of human gastric mucosal epithelial GES-1 cells and gastric cancer HGC-27,AGS,and SNU-1 cells was detected by cell adhesion assay.OGT inhibitor OSMI-1 and OGA inhibitor Thiamet G(TMG)were used to decrease or increase O-GlcNAc glycosylation modification levels of gastric cancer cells HGC-27 and SNU-1 cells,respectively,and their adhesion ability was detected by adhesion assay.Results:The mRNA expression levels of GFPT1,GNPNAT1,PGM3,OGT,and OGA were significantly elevated in pan-cancer tissues,especially gastric cancer,compared with those in adjacent tissues(P<0.05).Compared with HGC-27 and SNU-1 cells,the mRNA expressions of GFPT1,GNPNAT1,PGM3 and UAP1 in AGS cells of gastric cancer were higher,but the mRNA expressions of OGT and OGA were lower.The expression of GFPT1 protein was not significantly different among human gastric mucosal epithelial cells and three gastric cancer cell lines,but the expression of OGT and OGA protein was significantly increased in HGC-27 and SNU-1 cells compared with human gastric mucosal epithelial GES-1 cells(P<0.01).The relative expression level of O-GlcNAc in SNU-1 cells was significantly higher than that in GES-1 cells and HGC-27 and AGS cells(P<0.01).GSEA enrichment analysis indicated that OGT and OGA may regulate the adhesion ability of gastric cancer cells by regulating the level of O-GlcNAc modification.Decreasing the O-GlcNAc modification level of gastric cancer cells could significantly reduce the adhesion ability of gastric cancer cells.Conclusion:The level of O-GlcNAc glycosylation in gastric cancer HGC-27 and SNU-1 cells was significantly increased,which may enhance the adhesion ability of gastric cancer HGC-27 and SNU-1 cells by affecting the expression of related adhesion proteins in HBP.关键词
O连接的N-乙酰葡萄糖胺(O-GlcNAc)/胃癌/细胞黏附/己糖胺生物合成途径/细胞外基质Key words
O-linked N-acetylglucosamine(O-GlcNAc)/gastric cancer/cell adhesion/hexosamine biosynthesis pathway/extracellular matrix分类
临床医学引用本文复制引用
赵其杰,周时胜,娄文辉,钱晖,徐志伟..O-GlcNAc糖基化修饰对胃癌细胞黏附能力的影响[J].江苏大学学报（医学版）,2025,35(2):102-109,117,9.基金项目
国家自然科学基金资助项目(32000903) （32000903）
江苏大学高级人才启动基金资助项目(20JDG48) （20JDG48）
