Vitamin D promotes autophagy in AML cells by inhibiting miR-17-5p-induced Beclin-1 overexpression

Abstract

MicroRNA (miR)-17-5p has been investigated in many diseases as a regulator of disease progression and is highly expressed in acute myeloid leukemia (AML). However, potential mechanisms underlying the function of miR-17-5p in AML need more elucidation. MiR-17-5p expression was augmented, while 25(OH)D3 and Beclin-1 levels were decreased in AML patients with the highest risk for disease progression. MiR-17-5p, 25(OH)D3 and Beclin-1 were determined to be clinically important in AML based on ROC curve analysis. Higher miR-17-5p expression as well as lower 25(OH)D3 and Beclin-1 expression were relevant with poor prognosis in AML. In addition, miR-17-5p was negatively correlated with and bound to BECN1. Vitamin D was found to diminish cell proliferation and enhance autophagy. Finally, through rescue assays, miR-17-5p facilitated the ability of cell proliferation, inhibited autophagy and apoptosis by modulating Beclin-1 in HL-60 cells following the treatment of 4 μM vitamin D. Vitamin D promoted autophagy in AML cells by modulating miR-17-5p and Beclin-1.

Keywords: AML; Autophagy; Vitamin D; miR-17-5p.