Quercetin affects apoptosis and autophagy in pediatric acute myeloid leukaemia cells by inhibiting PI3K/AKT signaling pathway activation through regulation of miR-224-3p/PTEN axis

Abstract

Objective

The aim of this study was to investigate the mechanism by which quercetin (Que) affects apoptosis and autophagy in pediatric acute myeloid leukaemia (AML) cells by inhibiting the activation of the PI3K/AKT signaling pathway through the regulation of the miR-224-3p/PTEN axis.

Methods

Blood samples were collected from AML children and healthy volunteers. miR-224-3p and PTEN expression levels were measured. AML cells were pre-treated with Que. MiR-224-3p and PTEN expression levels in AML cells were altered via plasmid transfection. After intervention, PI3K/AKT phosphorylation, AML cell proliferation and apoptosis, concentrations of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in AML cell culture supernatant, apoptosis-related genes Bax and Bcl-2, and autophagy markers LC3-I and LC3-II were tested. The targeting relationship between miR-224-3p and PTEN was identified.

Results

MiR-224-3p expression was elevated in AML children, while PTEN was decreased. Que was available to accelerate AML cell apoptosis and restrain its autophagy. Que inhibited miR-224-3p expression and promoted PTEN expression. Upregulating miR-224-3p or downregulating PTEN weakened the effect of Que on AML cell apoptosis and autophagy. MiR-224-3p negatively modulated PTEN expression. Up-regulation of PTEN reversed the effects of up-regulation of miR-224-3p on apoptosis and autophagy in AML cells. In addition, Que inhibited PI3K/AKT signaling pathway activation, while up-regulation of miR-224-3p or down-regulation of PTEN could attenuate the inhibitory effect of Que on PI3K/AKT signaling pathway. Moreover, up-regulation of PTEN reversed the effect of up-regulation of miR-224-3p on the PI3K/AKT signaling pathway.

Conclusion

Que affects apoptosis and autophagy in pediatric AML cells by inhibiting PI3K/AKT signaling pathway activation through regulation of miR-224-3p/PTEN axis.