Exosomal encapsulation of miR-125a-5p inhibited trophoblast cell migration and proliferation by regulating the expression of VEGFA in preeclampsia

Abstract This study is aimed to examine the association between umbilical cord blood (UCB) derived exosomal microRNA (miRNA) with preeclampsia (PE) and to further explore the mechanism of a key differential gene (hsa-miR-125a-5p) in preeclampsia. Umbilical cord blood exosomal miRNA(exo-miRNA) from normal pregnant women and pregnant women with preeclampsia was processed via miRNA sequencing. Quantitative real-time polymerase chain reaction (QRT-PCR) was performed to assess the expression of miR-125a-5p in normal and PE placental tissues and peripheral blood derived exosomes in the third trimester. Human trophoblast cell line HTR8/SVneo was assigned as the negative control and miR-125a-5p mimics. QRT-PCR and Western blot were performed to identify the expressions of miR-125a-5p and vascular endothelial growth factor A (VEGFA). CCK8, flow cytometry, wound-healing and Transwell assays were used to analyze the effect of miR-125a-5p on HTR8/SVneo cell migration, proliferation, and cycle distribution. Tube formation was performed to estimate the angiogenesis ability of miR-125a-5p on HUVECs. In conclusion, miR-125a-5p expression in PE placental tissues was higher than in normal subjects, while the expression of VEGFA was lower in PE placental tissues. We then compared the miR-125a-5p mimics group with the negative control group and found that in the mimics group, the cell migration, proliferation and angiogenesis abilities were decreased, and more cells were arrested in the S stage. Our study systematically profiled the UCB exo-miRNA in normal and PE pregnant women and demonstrated that dysregulation of miR-125a-5p might affect HTR8/SVneo cell proliferation and migration and inhibit angiogenesis by regulating VEGFA, indicating that miR-125a-5p is involved in the progression of PE.