Background: Overexpression of the vascular endothelial growth factor (VEGF) is characterized in acute myeloid leukemia (AML), which stimulates endothelial cell mitogenesis and cell migration. MicroRNAs play a crucial role in the initiation and progression of malignancies. This study aimed to find the differential expression profiling of microRNAs that related with the expression level of VEGF in AML, and further explore the mechanism of VEGF in the course of AML.

Methods: The overexpression of VEGFa lentiviral vector LV-VEGFa-O or the knockdown of VEGFa lentiviral vector LV-VEGFa-shRNA or the empty lentiviral vector LV-NC was transfected into AML cells HL60 and U937. MicroRNAs was analysed by using a commercial microarray platform (miRCURY LNA™ v.18.0, Exiqon) for microRNAs. A set of selected microRNAs and VEGF mRNA were further analyzed by using quantitative real-time PCR in 45 bone marrow (BM) from primary AML patients.

Results: We have successfully constructed AML cell lines stably overexpressing VEGFa or knockdown VEGFa. Overexpression of VEGFa followed by a few changes of microRNAs profiling, that has-miR-1273f and has-miR-4679 were up-regulated, while eb-miR-BART10-3p and has-miR-3925-3p were down-regulated. However, knockdown of VEGFa significantly affected the expression profiling of microRNAs in AML cells. Thirty-three microRNAs were lower expression level than cells transfected with LV-NC (Figure 1). According to the expression level of VEGF, the AML patients were divided into two groups: VEGF-high group and VEGF-low group. We found five microRNAs (miR-20a, miR-93, miR-16-5p, miR-17 and miR-124-5p) were higher expression level in VEGF-high group than in VEGF-low group (p<0.05) (Figure 2).

Conclusion: Five microRNAs (miR-20a, miR-93, miR-16-5p, miR-17 and miR-124-5p) were positively correlated with VEGFa in AML. It is necessary to further explore the role of the selected microRNAs in the signal pathways of the regulation of VEGFa in the course of AML.

Figure 1
Figure 1.
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Figure 2
Figure 2.
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Disclosures

No relevant conflicts of interest to declare.

Topics:
leukemia, myelocytic, acute, micrornas, vascular endothelial growth factor a, gene expression profiling, molecular profiling, cancer, polymerase chain reaction, rna, messenger, bone marrow, cell lines

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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