MicroRNA-144 targets APP to regulate AML1/ETO+ leukemia cell migration via the p-ERK/c-myc/MMP-2 pathway

Abstract

Extramedullary infiltration (EMI) is common in patients with acute myeloid leukemia (AML) and is closely associated with the prognosis of disease. We previously reported that patients carrying the AML1/ETO (A/E) fusion gene and expressing the amyloid precursor protein (APP) tended to develop EMI, and had a poor prognosis. In the present study, the relapse-free survival (RFS) time and overall survival (OS) time were significantly lower in patients with EMI. The results demonstrated that the EMI incidence was significantly higher (P<0.05), while the RFS and OS rates were significantly lower (P<0.05), in patients with high APP expression. Kasumi-1 cells, which are A/E+, and the APP gene were used as the in vitro cell model to detect the mechanism of action in detail. Following the knockdown of APP expression, cell migration was significantly reduced (P<0.05). Furthermore, western blotting demonstrated that the protein expression of phosphorylated extracellular-signal-regulated kinase (p-ERK), matrix metalloproteinase-2 (MMP-2) and c-Myc was markedly reduced following interference of APP, while the expression of CXCR4 and MMP-9 was not altered. Kasumi-1 cells were co-cultured with p-ERK or c-Myc inhibitors and demonstrated that the APP/p-ERK/c-Myc/MMP-2 pathway was involved in signal transduction and regulation of cell migration. MicroRNA-144 (miR-144) mimics and transfected Kasumi-1 cells were generated. Reverse transcription-quantitative polymerase chain reaction and western blotting demonstrated that miR-144 was a negative regulator of APP. Taken together, the findings of the present study suggest that miR-144 negatively targets the APP gene and regulates cell migration via the APP/p-ERK/c-Myc/MMP-2 pathway.