中国肿瘤生物治疗杂志2026，Vol.33Issue(7)：763-775,13.DOI:10.3872/j.issn.1007-385X.2026.07.007
ST6GAL1与DUSP26蛋白在结直肠癌中的表达及其对M2型巨噬细胞极化与小鼠移植瘤进展的影响
Expression of ST6GAL1 and DUSP26 proteins in colorectal cancer and their effects on M2 macrophage polarization and mouse xenograft tumor progression
摘要
Abstract
Objective:To investigate the expression of β-galactoside α2,6-sialyltransferase 1(ST6GAL1)and dual-specificity phosphatase 26(DUSP26)in colorectal cancer(CRC),and their effects on macrophage polarization and tumor progression.Methods:A total of 126 patients with CRC were enrolled.Immunohistochemical staining was used to detect the expression of ST6GAL1 and DUSP26 proteins in cancer tissues and adjacent tissues.Western blotting,co-immunoprecipitation,exosome characterization,flow cytometry,ELISA,and immunofluorescence were performed to analyze the effects of ST6GAL1,DUSP26,and related signaling pathways on CRC cell-derived exosomes,M2 macrophage polarization,mitochondrial function,and endoplasmic reticulum stress.ST6GAL1 knockout(ST6GAL1-KO)and DUSP26 overexpression(DUSP26-OE)cell models were established using CRISPR/Cas9 and lentiviral systems,respectively.A mouse tumor model was used to evaluate the effects of combined ST6GAL1 knockout and DUSP26 overexpression(ST6GAL1-KO+DUSP26-OE)intervention on tumor growth,cell proliferation,and apoptosis.Results:The positive rate of ST6GAL1 protein was significantly higher in CRC tissues than in adjacent normal tissues,whereas the positive rate of DUSP26 protein was significantly lower in CRC tissues than in adjacent normal tissues(both P<0.001).ST6GAL1 protein expression was significantly higher in CRC cells than in normal colonic epithelial cells,whereas DUSP26 protein expression and the p-JNK/JNK and p-c-JUN/c-JUN ratios were significantly lower than those in normal colonic epithelial cells(all P<0.05).CRC cell-derived exosomes significantly promoted M2 macrophage polarization and upregulated the expression of the downstream proteins p-Syk,p-PI3K,and p-AKT,as well as the mitochondrial dysfunction-associated protein DRP1,and the endoplasmic reticulum stress-related proteins CHOP and GRP78(all P<0.01).Exosomes derived from DUSP26-OE or ST6GAL1-KO CRC cells inhibited these effects(P<0.05 or P<0.01).Animal experiments showed that tumor volume was significantly lower in the ST6GAL1-KO and DUSP26-OE groups than in the Vector group,and the combined ST6GAL1-KO and DUSP26-OE intervention group showed the most pronounced tumor-suppressive effect(all P<0.001).In the combined intervention group,the positive rate of the cell proliferation marker PCNA was significantly decreased,whereas the number of TUNEL-positive cells was significantly increased(P<0.05 or P<0.001).ST6GAL1-KO and DUSP26-OE significantly reduced the positive rates of GRP78 and DRP1 and the proportion of M2 macrophages in mice.Conclusion:In CRC,high ST6GAL1 expression may participate in the regulation of M2 macrophage polarization and stress-related protein expression by affecting exosomal sialylation levels,while low DUSP26 expression may weaken the negative regulation of ST6GAL1 expression mediated by JNK-related pathways.Combined intervention targeting both factors exerted a more pronounced inhibitory effect on xenograft tumor growth.关键词
β-半乳糖苷α2,6-唾液酸转移酶1/双特异性磷酸酶26/结直肠癌/巨噬细胞极化/外泌体Key words
β-galactoside α2,6-sialyltransferase 1(ST6GAL1)/dual-specificity phosphatase 26(DUSP26)/colorectal cancer(CRC)/macrophage polarization/exosome分类
医药卫生引用本文复制引用
石磊,赵磊,于生龙..ST6GAL1与DUSP26蛋白在结直肠癌中的表达及其对M2型巨噬细胞极化与小鼠移植瘤进展的影响[J].中国肿瘤生物治疗杂志,2026,33(7):763-775,13.基金项目
黑龙江省卫生健康委科研课题(2020-397) （2020-397）
