生物
癌变
结直肠癌
癌症研究
基因敲除
癌症
肿瘤进展
下调和上调
生物标志物
细胞生长
表型
微阵列分析技术
连环蛋白
遗传学
Wnt信号通路
细胞培养
基因
基因表达
作者
Nan Zhang,Si Liu,Junxuan Xu,Tingting Ning,Sian Xie,Li Min,Shengquan Zhu,Shutian Zhang,Shoumin Zhu
标识
DOI:10.1177/15353702221101810
摘要
The hexosamine biosynthetic pathway (HBP) is connected to abnormal N- and O-linked protein glycosylation in cancer, which performs critical roles in tumorigenesis. However, the regulation mechanisms of HBP and its role in colorectal cancer (CRC) progression remain unexplained. This study analyzed the expression level of phosphoglucomutase 3 (PGM3), a key enzyme in HBP, and identified its function in CRC cell lines. Analysis of publicly available CRC microarray data determined that PGM3 is upregulated in CRC tumor tissues. Furthermore, functional experiments emphasized the significant roles of PGM3 in facilitating CRC cell proliferation and migration. Mechanistically, we demonstrated that the activity of β-catenin in CRC was maintained by PGM3-mediated O-GlcNAcylation. PGM3 knockdown or inhibition of O-GlcNAc transferase decreased β-catenin activity and the expression levels of its downstream targets. Collectively, our findings indicate that PGM3 exhibits tumor-promoting roles by elevating O-GlcNAcylation level and maintaining β-catenin activity, and might serve as a prognostic biomarker and treatment target in CRC.
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