MicroRNA-628 inhibits the proliferation of acute myeloid leukemia cells by directly targeting IGF-1R.

Abstract

BackgroundA variety of microRNAs (miRNAs) are aberrantly expressed in acute myeloid leukemia (AML), and these dysregulated miRNAs perform crucial roles in tumorigenesis and progression of AML. miR-628-3p (miR-628), one of the miRNAs dysregulated in multiple types of human cancers, exerts antitumor roles in different cancer types. However, no specific study has explored the expression pattern and role of miR-628 in AML.Materials and methodsIn this study, RT-qPCR was performed to detect miR-628 expression in AML tissues and cell lines. CCK-8 assay, flow cytometry analysis and xenograft tumor experiment was carried out to determine the functions of miR-628 in AML cells. The possible mechanism underlying the activity of miR-628 in AML cells was also explored using a series of experiments.ResultsOur results revealed the downregulated expression of miR-628 in patients with AML and AML cell lines. Ectopic expression of miR-628 resulted in the inhibition of AML cell proliferation and induction of cell cycle arrest and apoptosis in vitro and attenuation of tumor growth in vivo. Insulin-like growth factor 1 receptor (IGF-1R) was identified as a direct target gene of miR-628 in AML cells. IGF-1R expression was upregulated in patients with AML and upregulation of IGF-1R expression inversely correlated with miR-628 level. Furthermore, IGF-1R knockdown imitated the tumor suppressive effect of miR-628 in AML cells. Restoration of IGF-1R expression abrogated the effects of miR-628 on the proliferation, cycle status, and apoptosis rate of AML cells. miR-628 inhibited the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) pathway in AML cells both in vitro and in vivo through the inhibition of IGF-1R expression.ConclusionOur results demonstrate that miR-628 exhibits antitumor effects in AML through the direct targeting of IGF-1R and regulation of PI3K/Akt pathway, suggestive of its potential role as a therapeutic target in patients with this aggressive hematological malignant tumor.