A correlation analysis of miRNA-34a and its predicted target genes in leukemia

Abstract

microRNA‑34a (miRNA‑34a) plays an important role in the pathogenesis of leukemia. This study aimed to explore its role in the proliferation of HL‑60 cells and the correlation with some of its predicted target genes: the cyclin‑dependent kinase 4 (CDK4), the oncogene MYB and the silent information regulator 1 (SIRT1). We first analyzed the expression of miR‑34a, CDK4, MYB and SIRT1 in peripheral blood samples from acute leukemia (AL) patients and healthy controls, and conducted a correlation analysis. HL‑60 cells were then transfected with miR‑34a and control 'scramble̓ miRNA, and quantitative RT‑PCR and western blotting were used to analyze the effects of the interfering sequence in HL‑60 cells. The expression of miR‑34a was significantly reduced in AL patients compared to healthy controls (P<0.01), and negatively correlated with the expression of CDK4 and MYB. Sub‑group analysis revealed that the expression of MYB was significantly lower in AL children <3 years old compared to those >3 years. Following the transfection of HL‑60 cells with miR‑34a, the mRNA level of CDK4, MYB and SIRT1 decreased by 53.2, 43.3 and 33.5%, respectively, compared to the control, similarly to the respective changes in protein levels. This study showed that the expression of miR‑34a negatively correlates with the expression of CDK4 and MYB in pediatric patients with acute leukemia. miRNA‑34a downregulates the expression of the CDK4, MYB and SIRT1 genes in vitro; it may thus represent a novel therapeutic target for acute leukemia.