Engaging of the mTOR signaling pathway by miR100 and miR101 in de novo acute myeloid leukemia

Abstract

Abstract Background: MicroRNAs (miRs) affect carcinogenesis and tumor progression by changing numerous cellular functions. miR-100 and miR-101 have been presented to be aberrantly expressed in acute leukemia. This study focused on their expression level in acute myeloid leukemia and their possible targets in molecular networks. Methods:miR-100 and miR-101 expression were analyzed in 21 patients with acute myeloid leukemia compared to 9 healthy controls by using quantitative RT-PCR in mononuclear cells of peripheral blood and bone marrow samples. The target of miR-100 and miR-101 were predicted with TargetScan,miRDB, and miRanda. Finally, the relationship of these microRNAs with mTOR/AKT/PI3Ksignaling pathway genes was investigated. Results: In this study, miR-100 was up-regulated (P value: 0.033; fold change: 6.8) whereas miR-101 (P value: 0.019; fold change : 0.61), mTOR (P value: 0.004; fold change: 0.56 ) and PI3KCA (P value <0.0001; fold change : 0.25) was downregulated in AML patients; there was a negative and positive correlation between the expression of miR-100 (r = -0.39, P value: 0.041) and miR-101 (r = 0.41, P value: 0.029) with the mTOR gene, while no meaningful correlation was seen between these miRs and the AKT1 and PI3KCAgenes. Conclusion: These data showed tumor suppressor role for both miR-100 and miR-101 via mTOR/AKT/PI3K signaling pathway, therefore it can be a favorable therapeutic target beside other ones. More investigation of the miR-100 and miR-101 network with other signaling pathways in AML is recommended.