Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells.
Daiana Luján VitaleIlaria CaonArianna ParnigoniIna SevicFiorella M SpinelliAntonella IcardiAlberto PassiDavide VigettiLaura D AlanizPublished in: Biomolecules (2021)
UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan-Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix.
Keyphrases
- cell cycle arrest
- cell death
- breast cancer cells
- induced apoptosis
- endoplasmic reticulum stress
- poor prognosis
- extracellular matrix
- oxidative stress
- pi k akt
- flow cytometry
- healthcare
- end stage renal disease
- binding protein
- signaling pathway
- chronic kidney disease
- skeletal muscle
- metabolic syndrome
- squamous cell carcinoma
- prognostic factors
- long non coding rna
- peritoneal dialysis
- weight loss
- simultaneous determination
- tandem mass spectrometry