Ecotropic viral integration site 1 regulates the progression of acute myeloid leukemia via MS4A3-mediated TGFβ/EMT signaling pathway.

Acute myeloid leukemia (AML) is a type of malignant tumor that is caused by malignant clone hematopoietic stem cells. The ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which is highly expressed in AML, and its expression level has been associated with poor prognosis of AML. Previous studies have indicated that Evi1 may regulate cell proliferation, differentiation and apoptosis by inhibiting the membrane-spanning-4-domains subfamily-A member-3 (MS4A3) gene in AML. The aim of the present study was to investigate the role of Evi1 in the progression of AML. The results revealed that Evi1 was overexpressed in leukemia cells compared with normal T lymphocytes. MicroRNAs (miR)-133 and -431 that target Evi1 were investigated, and it was observed that there was a low expression of miR-431 in AML. The transfection of miR-431 was able to decrease the promoter methylation levels of the Evi1 gene in AML cells. The transfection of miR-431 also suppressed the migration and invasion of AML cells. The present study revealed that the transfection of miR-431 mimic was able to downregulate MS4A3 expression in AML cells. Furthermore, the expression levels of transforming growth factor β (TGFβ) and epithelial-to-mesenchymal transition (EMT) markers fibronectin, α-smooth muscle actin, and vimentin were downregulated following the transfection of miR-431 in AML cells. The overexpression of MS4A3 was also able to suppress miR-431-mediated inhibition of the expression of TGFβ and EMT markers in AML cells. The addition of TGFβ inhibited the downregulation of EMT markers by transfection of miR-431 in AML cells. The transfection of miR-431 suppressed the migration and invasion of AML cells, which was also abolished by the addition of TGFβ. In conclusion, the results of the present study indicated that Evi1 may be a potential molecular target of leukemia therapy via MS4A3-mediated TGFβ/EMT signaling pathway.