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. 2020 Apr:93:94-100.
doi: 10.1016/j.placenta.2020.02.019. Epub 2020 Mar 5.

miR-150-5p mediates extravillous trophoblast cell migration and angiogenesis functions by regulating VEGF and MMP9

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miR-150-5p mediates extravillous trophoblast cell migration and angiogenesis functions by regulating VEGF and MMP9

Yu Zeng et al. Placenta. 2020 Apr.

Abstract

Introduction: miR-150-5p is involved in placenta function. Matrix metalloproteinases (MMPs) play important roles in migration and invasion of cells, while VEGF is the major contributing factor in angiogenesis, and they are related to miR-150-5p. However, the mechanism by which miR-150-5p regulates placental functions is not known. Thus, we investigated the influence of miR-150-5p on extravillous trophoblast function and the underlying epigenetic mechanism.

Methods: Real-time PCR were used to detect the miR-150-5p in the placenta of patients with preeclampsia and normal pregnant women. HTR-8/SVneo and JEG-3 cells were transfected with miR-150-5p inhibitor. Furthermore, we used CoCl2 to establish the hypoxia cell model. qRT-PCR and Western blot analysis were performed to detect VEGF and MMP9 expression levels in the transfected cells. Cell Counting Kit-8 assay was conducted to evaluate the proliferation ability. Wound-healing and transwell assays were used to detect the migration and invasion capacities. Tube formation assay was performed to evaluate the angiogenesis ability.

Results: miR-150-5p was up-regulated in the placenta of patients with preeclampsia. Inhibition of miR-150-5p significantly enhanced migration, invasion, and angiogenesis ability of both JEG-3 and HTR-8/SVneo cells. Similar results were seen in the hypoxic HTR-8/SVneo cell model. Moreover, mRNA and protein expression levels of VEGF and MMP9 were upregulated by the inhibition of miR-150-5p.

Discussion: miR-150-5p impacts placental cellular abilities, including migration, invasion, and angiogenesis of extravillous trophoblast cells. More importantly, miR-150-5p regulates VEGF and MMP9 expression. The results suggest that miR-150-5p may have an impact on placenta functions.

Keywords: Extravillous trophoblast; Hypoxia; MMP9; Preeclampsia; VEGF; miR-150-5p.

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