Pyridoxine 5'-phosphate oxidase is a novel therapeutic target and regulated by the TGF-beta signalling pathway in epithelial ovarian cancer.

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Zhang L, Zhou D, Guan W, Ren W, Sun W, Shi J, Lin Q, Zhang J, Qiao T, Ye Y, Wu Y, Zhang Y, Zuo X, Connor KL, Xu G

Pyridoxine 5'-phosphate oxidase is a novel therapeutic target and regulated by the TGF-beta signalling pathway in epithelial ovarian cancer.

Cell Death Dis. 2017 Dec 13;8(12):3214. doi: 10.1038/s41419-017-0050-3.

PubMed ID

29238081 [ View in PubMed

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Abstract

Pyridoxine 5'-phosphate oxidase (PNPO) is an enzyme that converts pyridoxine 5'-phosphate into pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 implicated in several types of cancer. However, the role of PNPO and its regulatory mechanism in epithelial ovarian cancer (EOC) are unknown. In the present study, PNPO expression in human ovarian tumour tissue and its association with the clinicopathological features of patients with EOC were examined. Further, the biological function of PNPO in EOC cells and in xenograft was evaluated. We demonstrated for the first time that PNPO was overexpressed in human EOC. Knockdown of PNPO induced EOC cell apoptosis, arrested cell cycle at G2/M phase, decreased cell proliferation, migration and invasion. Xenografts of PNPO-shRNA-expressing cells into the nude mouse attenuated tumour growth. PNPO at mRNA and protein levels in EOC cells was decreased after transforming growth factor-beta1 (TGF-beta1) treatment. The inhibitory effect of TGF-beta1 on PNPO expression was abolished in the presence of SB-431542, a TGF-beta type I receptor kinase inhibitor. Moreover, we found that TGF-beta1-mediated PNPO expression was at least in part through the upregulation of miR-143-3p. These data indicate a mechanism underlying PNPO regulation by the TGF-beta signalling pathway. Furthermore, PLP administration reduced PNPO expression and decreased EOC cell proliferation, suggesting a feedback loop between PLP and PNPO. Thus, our findings reveal that PNPO can serve as a novel tissue biomarker of EOC and may be a potential target for therapeutic intervention.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Pyridoxine phosphate	Pyridoxine-5'-phosphate oxidase	Protein	Humans	Unknown	Substrate	Details