Downregulation of UDP-glucose 6-dehydrogenase predicts adverse prognosis in colorectal cancer and promotes tumorigenesis

Backgrounds: UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism and a key mediator in several cancer developmental signaling pathways. However, the expression and function of UGDH in colorectal cancer (CRC) are unclear. Method: Bioinformatics analysis was conducted to research the expression, diagnosis, prognosis, functional enrichment, genetic alterations, and immune characteristics of UGDH in CRC. The UGDH gene was knocked down in HCT-8 cells. CCK8 and cell wound scratch assays were further performed in UGDH wild-type and knocked-down HCT-8 cells. Results: UGDH is remarkably decreased in CRC compared to normal tissues, which predicts a poor prognosis. UGDH’s lower expression is associated with a high gene promoter methylation level and genome deletion. UGDH expression is proportional to immune cell infiltration and immune-related genes. UGDH expression is correlated to the p53 signaling pathway. Compared to the normal colonic epithelial cells, UGDH is downregulated in CRC cells. Knockdown of UGDH in HCT-8 cells promotes the proliferation and migration ability. Conclusions: UGDH could be useful as a valuable prognostic biomarker and potential therapeutic target in CRC. UGDH could inhibit the proliferation and migration of CRC cells, possibly by modulating the p53 signaling pathway.