Effects of circular RNA circOMA1 on cell proliferation and apoptosis of children with acute myeloid leukemia / 中华实用儿科临床杂志

ABSTRACT

Objective:To investigate the expression of circular RNA circOMA1 in children with acute myeloid leukemia (AML) and to investigate the effect and mechanism of circOMA1 on the cell proliferation and apoptosis of human acute monocytic leukemia cells (THP-1).Methods:Bone marrow samples of 14 children with AML at the initial diagnosis and after complete remission were collected as the initial diagnosis group and remission group, and bone marrow samples from 10 children without tumor or malignant blood disease in the same hospital and the same period were enrolled as the control group.Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of circOMA1, miR-145 and myelocytomatosis viral oncogene homolog (MYC) mRNA in clinical AML samples and THP-1 cell line.The cells transfected with THP-1 were divided into groups, the cells transfected with circOMA1 alone (circOMA1 high expression group) were transfected with pcDNA3.1 empty vector cells as control (pcDNA3.1 control group); the cells co transfected with circOMA1 and miR-145 (circOMA1+ miR-145 group) were treated with pcDNA3.1 and miR-NC co transfected cells were used as control (pcDNA3.1+ miR-NC group, circOMA1+ miR-NC group). Cell counting kit (CCK8) was adopted to detect the effects of circOMA1 and miR-145 on the cell proliferation of THP-1.The effects of circOMA1 and miR-145 on cell apoptosis of THP-1 were detected using flow cytometry, and the effects of circOMA1 and miR-145 on MYC protein expression was detected via Western blot.The comparison between groups was analyzed by independent sample t-test or paired sample t-test, and the correlation was analyzed by Pearson correlation. Results:The expression of circOMA1 in the initial diagnosis group(4.408±3.607) was significantly increased compared with that in the control group (0.998±0.560) ( t=2.946, P<0.01); the expression of circOMA1 in remission group(1.582±0.950) was significantly decreased compared with that in the initial diagnosis group( t= 3.628, P<0.01). The THP-1 cell experiments showed that compared to the pcDNA3.1 control group, the expression of miR-145 in the circOMA1 high expression group decreased ( t= 4.21, P<0.05), cell proliferation was enhanced at 72 h and 96 h ( t=5.46, 7.40, all P<0.05), apoptosis was inhibited( t=6.44, P<0.01). The expression of MYC protein in circOMA1+ miR-NC group was higher than that of pcDNA3.1+ miR-NC group( t=5.72, P<0.01), the expression of MYC protein in circOMA1+ miR-145 group was lower than that in circOMA1+ miR-NC group ( t=4.56, P<0.05); at 72 h and 96 h, the cell proliferation level of circOMA1+ miR-NC group was higher than that of pcDNA3.1+ miR-NC group ( t=5.77, 7.30, all P<0.05), the level of cell proliferation in circOMA1+ miR-145 group was lower than that in circOMA1+ miR-NC group ( t=4.66, 6.17, all P<0.05); the apoptosis rate of circOMA1+ miR-145 group was higher than that of circOMA1+ miR-NC group ( t=4.25, P<0.05). circOMA1 expression was negatively correlated with miR-145 expression ( r=-0.62, P=0.016) and positively correlated with MYC gene expression ( r=0.64, P=0.013) in clinical samples. Conclusions:circOMA1 is highly expressed in children with AML, and can promote AML cell proliferation and inhibit apoptosis through miR-145/MYC pathway, which provides a basis for AML therapy and diagnosis.