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Overexpression of miR‑21 is involved in acute monocytic leukemia‑associated angiogenesis by targeting IL‑12.

He X.P., Chen P., Yang K., Liu B., Zhang Y., Wang F., Guo Z., Liu X.D., Lou J.X., Chen H.R.

Angiogenesis is important in pathophysiological processes, including the pathogenesis of acute monocytic leukemia (AML). MicroRNA‑21 (miR‑21) is overexpressed and exhibits oncogenic activity in cancer. However, the biological mechanism underlying the effect of miR‑21 in AML remains to be fully elucidated. In the present study, the expression levels of miR‑21 and vascular endothelial growth factor (VEGF) were determined in 26 patients with AML and 28 healthy individuals. The secretion of VEGF was also measured following the transfection of THP‑1 cells with miR‑21 mimic or inhibitor. The supernatants of the THP‑1 cells, which were transfected with miR‑21 mimic, inhibitor or small interfering RNA (si)VEGF, respectively, were used to incubate human umbilical vein endothelial cells (HUVECs), following which tube formation of the HUVECs was measured. miR‑21 targets were predicted using a biological target prediction website and confirmed using a luciferase assay. The effects of interleukin (IL)‑12 were investigated by examining the tube formation of HUVECs and the secretion of VEGF following recombinant human (rh) IL‑12 pretreatment. The results revealed that miR‑21 and VEGF expression was significantly increased in the peripheral blood monocytes of the patients, compared with the healthy controls. There was negative correlation between the expression of IL‑12 and miR‑21 in the serum of patients with AML. Furthermore, supernatant VEGF levels from the miR‑21 mimic‑transfected THP‑1 cells were increased, whereas a decreasing trend was observed in the miR‑21 inhibitor group. The angiogenic ability of the HUVECs pretreated with supernatant from the THP‑1 cells transfected with miR‑21 mimic was higher, and was lower in THP‑1 cells co‑transfected with miR‑21 mimic and siVEGF, compared with the miR‑21 mimic only group. A luciferase assay demonstrated that IL‑12 was the direct target of miR‑21, and the level of IL‑12 in the supernatant of THP‑1 cells transfected with miR‑21 mimic was increased. IL‑12 pretreatment increased VEGF expression and angiogenic ability in HUVECs. The inactivation of miR‑21 or activation of its target gene may be a potential therapeutic strategy in human AML.

Mol Med Rep 18:4122-4128(2018) [PubMed] [Europe PMC]

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