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

• Published in: Molecular and cellular biochemistry Vol. 476; no. 11; pp. 3951 - 3962
• Main Authors: Wang, Weijia, Liu, Jing, Chen, Kang, Wang, Juan, Dong, Qian, Xie, Jinye, Yuan, Yong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-11-2021; Springer; Springer Nature B.V
• Subjects: Acute myeloid leukemia; Adult; Alfacalcidol; Analysis; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Beclin-1 - antagonists & inhibitors; Beclin-1 - biosynthesis; Beclin-1 - genetics; Beclin-1 - metabolism; Biochemistry; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Calcifediol; Calciferol; Cardiology; Case-Control Studies; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Female; Humans; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Life Sciences; Male; Medical Biochemistry; Medical research; Medicine, Experimental; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; Middle Aged; miRNA; Myeloid leukemia; Oncology; Phagocytosis; ROC Curve; Survival Rate; Vitamin D; Vitamin D - pharmacology; Vitamins - pharmacology; AML; miR-17-5p; Vitamin D; Autophagy
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-021-04208-z

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.