Possible role of glucose-6-phosphatase 3 in the pathogenesis of uterine leiomyomas

Abstract

Background and aim: Glucose-6-phosphatase catalytic subunit 3 (G6PC3) has been recently described as a metabolite repair enzyme involved in the disposal of the phosphorylated glucose analog 1,5-anhydroglucitol-6-phosphate (1,5AG6P). This function is especially relevant in neutrophils; indeed, G6PC3 deficiency leads to neutropenia as the accumulated metabolite 1,5AG6P inhibits the first step of glycolysis. Like neutrophils, tumoral metabolism also mainly relies on glycolysis, and we wondered if G6PC3 is expressed in uterine leiomyoma samples and if it can eventually have a role in the pathogenesis of these tumors. Understanding the complex pathophysiology of leiomyomas is a prerequisite to develop new therapeutic strategies. Methods: We used human uterine leiomyoma and matched myometrial samples. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) were performed. Results: Immunohistochemical analysis has not evidenced appreciable differences between pathologic versus normal tissue samples. Indeed, qPCR analysis suggests a higher expression of G6PC3 in human uterine leiomyoma than in matched myometrial samples. Conclusion: A targeted therapeutic inhibition of G6PC3 in uterine leiomyoma samples is a potential strategy to slow down tumor growth.

Keywords

• G6PC3
• G6PT
• 1,5-Anhydroglucitol-6-phosphate
• Glycolysis
• Uterine leiomyomas