MiR-454-3p promotes apoptosis and autophagy of AML cells by targeting ZEB2 and regulating AKT/mTOR pathway

Background: miR-454-3p is considered to have a crucial role in Cancer progression, but the potential involvement in acute myeloid leukemia (AML) remains unclear.

Methods: Expression of miR-454-3p and ZEB2 mRNA and protein were quantified in AML cell lines. Cells were transfected with miR-454-3p inhibitor or mimic and cell growth was assessed by colony formation and CCK-8 assays and the cell cycle, Apoptosis and Autophagy were investigated by Western blotting, flow cytometry, immunofluorescence and 3-methyladenine (3-MA) treatment.

Results: miR-454-3p expression was attenuated in AML cells. miR-454-3p overexpression attenuated cell growth and stimulated cell cycle arrest, Apoptosis and Autophagy. Dual-luciferase reporter assays and bioinformatics analysis showed that AML progression was inhibited when miR-454-3p regulated ZEB2, an effect confirmed by rescue assays. 3-MA reduced the autophagy-inducing effect of ZEB2 knockdown and indicated that Autophagy induced Apoptosis. miR-454-3p downregulated p-mTOR/p-AKT levels in AML cells.

Conclusion: The novel role of miR-454-3p as a tumor inhibitor in AML via regulation of the ZEB2/Akt/mTOR axis was demonstrated, indicating miR-454-3p as a potential new molecular target for AML.

AKT/mTOR pathway; AML; ZEB2; apoptosis; autophagy; miR-454-3p.