UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology

Price, Meghan J.; Nguyen, Annee D.; Byemerwa, Jovita K.; Flowers, Jasmine; Baëta, César D.; Goodwin, C. Rory

doi:10.18632/oncotarget.28514

Cited by 7 publications

(1 citation statement)

References 54 publications

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“…The protein encoded by this gene is a rate-limiting enzyme that converts UDP-glucose to UDP-glucuronate, thereby participating in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated compounds are common components of the extracellular matrix and likely play roles in signal transduction, cell migration, cancer growth, and cancer metastasis [7]. The role of UGDH in cancer has received extensive attention from researchers in recent years.…”

Section: Introductionmentioning

confidence: 99%

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Cao,

Li,

Xue

et al. 2024

Preprint

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Backgrounds: Abnormalities in glycometabolism lead to carcinogenesis. UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism and acts as a key mediator in several cancer developmental signaling pathways. In this study, our objective is to offer a more systematic and comprehensive elucidation of the involvement of UGDH in the onset and advancement of various malignancies via an in-depth analysis of UGDH in cancer contexts. Method: We investigated the role of UGDH in cancers using the Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. And analyzed data using various R packages and websites, including TISIDB, cBioPortal, STRING, Cytoscape, GSCALite, and CancerSEA. A rat hepatocellular carcinoma (HCC) model was established using intraperitoneal injection of diethylnitrosamine. Hematoxylin-Eosin (HE) staining, MASSON staining, and KI67 immunohistochemistry of liver tissues were performed. Real-time quantitative PCR (qRT-PCR) and western blotting (WB) were used to detect the expression of UGDH. UGDH gene was knocked down in Huh7 cells, and CCK8 and nude mice tumor xenograft assays were further performed. Results: UGDH high expression is associated with poor clinical outcomes in hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma. And differentially expressed across molecular and immune subtypes. UGDH was primarily involved in the pentose and glucuronate interconversion pathway. Its expression positively correlated with T helper, Tcm, and Th2 cells in most cancers. Moreover, experimental results demonstrated that UGDH expression is elevated in liver cancer and promotes the proliferation of HCC. Conclusions: Our study elucidates that UGDH could be used as a valuable prognostic biomarker and potential therapeutic target in many cancers, especially liver and lung cancer. UGDH could promote the proliferation of HCC cells, possibly by modulating the pentose and glucuronate interconversion pathway.

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Section: Introductionmentioning

confidence: 99%

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Cao,

Li,

Xue

et al. 2024

Preprint

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Deciphering the cell type-specific and zonal distribution of drug metabolizing enzymes, transporters, and transcription factors in livers of mice by single cell transcriptomics

Lim,

Klaassen,

Cui

2024

Drug Metabolism and Disposition

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A role for pH dynamics regulating transcription factor DNA binding selectivity

Kisor,

Ruiz,

Jacobson

et al. 2024

Preprint

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Intracellular pH (pHi) dynamics regulates diverse cell processes such as proliferation, dysplasia, and differentiation, often mediated by the protonation state of a functionally critical histidine residue in endogenous pH sensing proteins. How pHi dynamics can directly regulate gene expression and whether transcription factors can function as pH sensors has received limited attention. We tested the prediction that transcription factors with a histidine in their DNA binding domain (DBD) that forms hydrogen bonds with nucleotides can have pH-regulated activity, which is relevant to more than 85 transcription factors in distinct families, including FOX, KLF, SOX and MITF/Myc. Focusing on FOX family transcription factors, we used unbiased SELEX-seq to identify pH-dependent DNA binding motif preferences, then confirm pH-regulated binding affinities for FOXC2, FOXM1, and FOXN1 to a canonical FkhP DNA motif that are 2.5 to 7.5 greater at pH 7.0 compared with pH 7.5. For FOXC2, we also find greater activity for an FkhP motif at lower pHi in cells and that pH-regulated binding and activity are dependent on a conserved histidine (His122) in the DBD. RNA-seq with FOXC2 also reveals pH-dependent differences in enriched promoter motifs. Our findings identify pH-regulated transcription factor-DNA binding selectivity with relevance to how pHi dynamics can regulate gene expression for myriad cell behaviours.

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UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology

Cited by 7 publications

References 54 publications

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Deciphering the cell type-specific and zonal distribution of drug metabolizing enzymes, transporters, and transcription factors in livers of mice by single cell transcriptomics

A role for pH dynamics regulating transcription factor DNA binding selectivity

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