microRNA‑646 inhibits angiogenesis of endothelial progenitor cells in pre‑eclamptic pregnancy by targeting the VEGF‑A/HIF‑1α axis
- Dirong Dong
- Yimin Khoong
- Yunzhen Ko
- Yuanzhen Zhang
Affiliations: Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
- Published online on: June 24, 2020 https://doi.org/10.3892/etm.2020.8929
Copyright: © Dong
et al. This is an open access article distributed under the
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Pre-eclampsia is a complication that occurs during pregnancy, the pathological feature of which is a change in vascular endothelial homeostasis. microRNA (miR)‑646 is an anti‑angiogenic miRNA that has been indicated to exhibit potential anti‑angiogenic effects in endothelial cells cultured in vitro and in ischemia‑induced angiogenesis. However, whether miR‑646 has therapeutic potential in placental angiogenesis in pre‑eclampsia remains to be determined. In the current study, human peripheral blood‑derived endothelial progenitor cells (EPCs) were isolated to study the coordination between miR‑646, vascular endothelial growth factor (VEGF)‑A and hypoxia‑inducible factor (HIF)‑1α expression in preeclampsia EPCs. EPCs were isolated from human peripheral blood to demonstrate a potential interaction between miR‑646 and targets (VEGF‑A) in vitro. The number of EPCs and the expression of miR‑646 in patients with preeclampsia was detected, and the effects of miR‑646 on EPC function and preeclampsia angiogenesis was assessed. Clinical specimens demonstrated that miR‑646 expression was enhanced in pregnancy with preeclampsia. The results indicated that miR‑646 suppressed EPCs multiplication, differentiation and migration. miR‑646 was observed to exert an anti‑angiogenic function by suppressing the expression of angiogenic cytokines VEGF‑A and HIF‑1α. Additionally, luciferase results displayed that miR‑646 downregulated VEGF‑A expression by directly binding to a specific sequence in its 3'‑untranslated region. The results of the current study demonstrated that the miR‑646/VEGF‑A/HIF‑1α axis is significant for angiogenic properties of EPCs in vitro and in vivo placental vasculogenesis. The results of the present study provide a new insight into microRNA regulation of vessel homeostasis and angiogenesis, and a basis for alternative treatments for patients with pre‑eclampsia.