MiR-16 induces G1 cell cycle arrest and apoptosis in acute myeloid leukemia cells

Abstract

ObjectiveAcute promyelocytic leukemia is a subset of acute myeloid leukemia bearing t (15; 17) chromosomal aberration. The expression of this gene results in PML/RARα recombinant protein. MicroRNAs are a group of small noncoding RNA molecules regulating the expression of genes by targeting their mRNA. MiR-16-1 regulates several cellular functions and acts as a tumor suppressor. The aim of this study was transduction of NB4 cells with miR-16-1 lentiviral as well as evaluation of changing expressions of Bcl-2 gene and apoptosis in cells due to the function of miR-16-1. Materials and methodsIn this study, NB4 cells were transduced with a miR-16-1 lentiviral vector, and cytotoxic effect of this miRNA on cells was investigated using MTT assay. QReal-Time PCR measured the expression level of Bax and Bcl-2 genes before and after treatment. Annexin-PE/7ADD and caspase 3 kits were used to assess the apoptosis induced by increased expression of miR-16-1. ResultsMTT assay showed that miR-16-1 was able to reduce the proliferation and activity of NB4 cells significantly. Study of changing the expression of Bax and Bcl-2 genes in the cells treated with miR-16-1 showed that miR-16-1 had not caused a significant difference. However, miR-16-1 led to the arrest of cells in the G1 phase, and a significant increase was observed in caspase-3 activity in the cells transduced with miR-16-1, which can activate another pathway to induce apoptosis. ConclusionThe data suggest that miR-16-1 induced apoptosis and arrested cell cycle of NB4 cells in G1 phase, which can have therapeutic effects in leukemia.