中国病理生理杂志2025，Vol.41Issue(2)：209-218,10.DOI:10.3969/j.issn.1000-4718.2025.02.001
COSMC对胃癌细胞干细胞样特性的影响及机制研究
Impact of COSMC on stem cell-like properties of gastric cancer cells and its underlying mechanisms
摘要
Abstract
AIM:To investigate the impact of core 1 β3-galactosyltransferase-specific molecular chaperone(COSMC)on the stem cell-like properties of gastric adenocarcinoma cells,and to elucidate its underlying mechanism.METHODS:GEPIA(Gene Expression Profiling Interactive Analysis),TIMER(Tumor IMmune Estimation Resource),Wei Sheng Xin platform,UALCAN(University of Alabama at Birmingham Cancer Data Analysis Portal)and UCSC(Uni-versity of California,Santa Cruz)Xena databases were employed to analyze COSMC expression levels across various carci-noma types.The COSMC expression in gastric cancer tissues and cell lines was evaluated using Western blot analysis.Transfection of small interfering RNA was used to knock down COSMC in MKN-45 cell line.In vitro experiments were con-ducted to explore the relationship between the COSMC expression and the stem cell-like properties of gastric cancer.The qPCR,sphere formation assay,soft agar colony formation assay and CCK-8 assay were used to evaluate the effect of COSMC on the stem cell-like properties of gastric cancer cells.Tn+and Tn-cells were isolated using Vicia villosa lectin(VVL)-conjugated immunomagnetic beads to investigate the influence of Tn structure on the stem cell-like characteristics of gastric cancer cells.Finally,the effect of COSMC knockdown on the mitogen-activated protein kinase(MAPK)signal-ing pathway was evaluated by Western blot analysis.RESULTS:(1)The COSMC exhibited differential expression across pancarcinoma,gastric cancer tissues and gastric cancer cell lines,with elevated expression levels in gastric cancer tissues and gastric cancer cell lines compared with normal tissues and gastric epithelial cell line.(2)Knockdown of COSMC sig-nificantly down-regulated the mRNA levels of stem cell markers NANOG,OCT-4 and CD44 in gastric cancer cells,re-duced the efficiency of soft agar colony formation and sphere formation,and increased the sensitivity of the cells to 5-fluo-rouracil(5-FU).(3)The efficiency of tumor sphere formation and soft agar colony formation in Tn-cells,and the resis-tance to 5-FU were significantly higher than those in Tn+cells.(4)Knockdown of COSMC decreased the protein levels of MAPK signaling pathway-related molecules,including c-Jun N-terminal kinase(JNK),p38 and phosphorylated extracel-lular signal-regulated kinase(p-ERK).CONCLUSION:The COSMC has the potential to enhance the stem cell-like properties of gastric cancer cells,which was likely mediated through the activation of the MAPK signaling pathway.关键词
COSMC蛋白/胃癌干细胞/Tn结构/糖基化Key words
COSMC protein/gastric cancer stem cells/Tn structure/glycosylation分类
医药卫生引用本文复制引用
李文彦,张雨晗,贺雨萱,雷一鸣,张越诚,张静,孙凌波..COSMC对胃癌细胞干细胞样特性的影响及机制研究[J].中国病理生理杂志,2025,41(2):209-218,10.基金项目
国家自然科学基金资助项目(No.22264023) （No.22264023）
陕西省自然科学基础研究计划资助项目(No.2024JC-YBQN-0150) （No.2024JC-YBQN-0150）
陕西省卫生健康科研基金资助项目(No.2022E019) （No.2022E019）
陕西省教育厅专项科研计划资助项目(No.22JK0614) （No.22JK0614）
