Effect Of MiR-520a Targeting The Expression Of MCM3 On The Cell Proliferation Of Acute B Lymphoblastic Leukemia Cells

Objective: The abnormal expression profile of micro RNAs(miRNAs)plays an important role in many types of cancer,including leukemia.miR-520 a acts as a tumor suppressor in ovarian cancer,lung cancer,chronic myeloid leukemia and other cancers.Up-regulation of miR-520 a in acute myeloid leukemia may predict poor prognosis,but the role of miR-520 a has not been reported in acute lymphoblastic leukemia.The aim of this study was to investigate the expression of miR-520 a in acute B lymphoblastic leukemia cells and its effect on the proliferation of leukemia cells.Methods: The expression of miR-520 a was detected by real-time fluorescence quantitative PCR in the the bone marrow lymphocytes from both non-malignant hematological tumor and acute lymphocytic leukemia patients,normal peripheral blood lymphocytes and acute lymphocytic leukemia cells.The cell proliferation was observed by CCK-8 assay.Western blot was used to detect the expressions of MCM3 in different tissues and cells with or without miR-520 a mimics’ transfection.Bioinformatics analysis showed that MCM3 was the target gene of miR-520 a,and its target site was predicted.Dual-luciferase reporter assay was used to detect the effect of miR-520 a on the transcriptional activity of MCM3.In the miR-520 a mimics group,the overexpression plasmid of MCM3 was used to carry out the complement experiment,and the cell proliferation was observed.Results: Compared with normal tissues and cells,the expression level of miR-520 a in bone marrow lymphocytes of patients with acute lymphoblastic leukemia and BALL-1 cell lines were significantly lower(P<0.001).The proliferation abilities of BALL-1 cells were decreased by the overexpression of miR-520a(P<0.001).Meantime,compared with normal tissues and cells,the expression levels of MCM3 in bone marrow lymphocytes of patients with acute lymphoblastic leukemia and BALL-1 cell lines were significantly increased(P<0.001).The overexpression of miR-520 a decreased the protein expression of MCM3(P<0.001).The indirect and direct experiments confirmed that miR-520 a could target the 3’UTR region of MCM3.miR-520 a mimics can decrease the proliferation of BALL-1 cells,and the overexpression of MCM3 can increase the expression level of MCM3 and the ability of cell proliferation.Conclusion : Overexpression of miR-520 a can significantly downregulate the expression of MCM3 protein;miR-520 a may inhibit the proliferation ability of acute B lymphoblastic leukemia cells by downregulating the expression of MCM3.Furthermore,it may provide a new target for the treatment of acute B lymphoblastic leukemia.