Abstract
Acute myeloid leukemia (AML) is as a highly aggressive and heterogeneous hematological malignancy. MiR-20a-5p has been reported to function as an oncogene or tumor suppressor in several tumors, but the clinical significance and regulatory mechanisms of miR-20a-5p in AML cells have not been fully understood. In this study, we found miR-20a-5p was significantly decreased in bone marrow from AML patients, compared with that in healthy controls. Moreover, decreased miR-20a-5p expression was correlated with risk status and poor survival prognosis in AML patients. Overexpression of miR-20a-5p suppressed cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis in two AML cell lines (THP-1 and U937) using CCK-8 assay and flow cytometry analysis. Moreover, miR-20a-5p overexpression attenuated tumor growth in vivo by performing tumor xenograft experiments. Luciferase reporter assay and western blot demonstrated that protein phosphatase 6 catalytic subunit (PPP6C) as a target gene of miR-20a-5p was negatively regulated by miR-20a-5p in AML cells. Furthermore, PPP6C knockdown imitated, while overexpression reversed the effects of miR-20a-5p overexpression on AML cell proliferation, cell cycle G1/S transition and apoptosis. Taken together, our findings demonstrate that miR-20a-5p/PPP6C represent a new therapeutic target for AML and a potential diagnostic marker for AML therapy.
Highlights
Acute myeloid leukemia (AML), as a highly aggressive and heterogeneous hematological malignancy, is characterized by abnormal growth of bone marrow stromal cells and undifferentiated myeloid progenitor cells in the bone marrow and peripheral blood [1, 2]
To explore the potential role of miR-20a-5p in AML development, the expression of miR-20a5p was first analyzed by quantitative real time PCR in bone marrow from 61 AML patients and healthy controls
All AML patients were allocated to high and low miR-20a-5p expression group based on the median value, which were applied to research the correlation between miR-20a-5p expression and clinical features
Summary
Acute myeloid leukemia (AML), as a highly aggressive and heterogeneous hematological malignancy, is characterized by abnormal growth of bone marrow stromal cells and undifferentiated myeloid progenitor cells in the bone marrow and peripheral blood [1, 2]. The principal therapeutic approaches, including chemotherapy, targeted therapy, and hematopoietic stem cell transplantation, have greatly improved the therapeutic outcomes of patients with AML [3, 4]. The prognosis and outcomes remain still poor in AML patients at advanced stage, which might be correlated with major problems, such as serious infection and bleeding [5,6,7]. It is of great importance to elucidate the molecular mechanisms responsible for the progression of AML.
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