Modulation of human miR-17-3p expression by methyl 3-O-methyl gallate as explanation of its in vivo protective activities

Abstract

Scope: Methyl-3-O-methyl gallate (M3OMG) possesses in vivo antioxidant activity due to the partial restoration of the antioxidant enzymes, whose expression is altered in oxidative stress. Literature data suggest that miR-17-3p is a microRNA involved in the regulation of cellular redox status, interfering with transcription of the mRNAs responsible for the synthesis of antioxidant enzymes. To obtain deeper insight into the potential mechanism of action of M3OMG, the aim of this study was to investigate its effect on the expression levels of miR-17-3p in human cells.

Methods and results: Peripheral blood mononuclear cells and EVC-304 cells were treated with increasing subtoxic concentrations of M3OMG. The expression levels of miR-17-3p, extracted from cells and exosomes, were determined by quantitative real-time PCR. M3OMG induced a decrease in the miR-17-3p levels, and an increase in the levels of mRNA coding for the antioxidant enzymes, when compared to the control samples. Differently, in exosomes the expression levels of miR-17-3p were depended on the compound, its concentration, and the type of cell.

Conclusion: These results suggest a potential mechanism of action of M3OMG that, inducing the reduction of the levels of miR-17-3p and the increase of mRNA coding for antioxidant enzymes, allows to these latter to perform their protective effects.

Keywords: Antioxidant enzymes; Human cells; Methyl 3-O-methyl gallate; MicroRNA; miR-17-3p expression level.