Exosomal microRNA‑302a promotes trophoblast migration and proliferation, and represses angiogenesis by regulating the expression levels of VEGFA in preeclampsia

Abstract

The global morbidity rate of preeclampsia (PE) is 3-7, and 10-20% of maternal deaths are associated with PE. However, the mechanism of its pathogenesis remains unknown. The aim of the present study was to examine the relationship between microRNA-302a (miR-302a) and PE. Firstly, the relative expression levels of miR-302a in placental tissues from patients with PE and normal controls were analyzed using reverse transcription-quantitative PCR. miR-302a expression was upregulated in PE tissues, particularly in severe PE. Subsequently, HTR-8/SVneo cells were transfected with miR-302a vectors to overexpress miR-302a. The overexpression of miR-302a markedly promoted cell proliferation, colony formation, migration and invasion in vitro. Subsequently, the present study examined the function of exosomes secreted by HTR-8/SVneo cells transfected with miR-302a vectors. Compared with the negative control vector group, miR-302a expression was markedly increased in exosomes in the miR-302a overexpression group. Additionally, exosomes with miR-302a overexpression had repressed HUVEC invasion and ring formation. The luciferase reporter assay indicated that VEGFA was a direct target of miR-302a, and miR-302a expression was negatively correlated with VEGFA expression. In conclusion, the present results demonstrated that upregulation of miR-302a may promote HTR-8/SVneo cell proliferation, migration and invasion, and repress angiogenesis by targeting VEGFA, indicating that miR-302a may be a potential target for the development of PE therapies.

Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis

“…Some exosomal miRNAs are reported to modulate angiogenesis. For example, the migration and proliferation of trophoblasts are improved, and the angiogenesis of HUVEC is inhibited, by exosomal miR-302a [ 263 ].…”

Omics insights into extracellular vesicles in embryo implantation and their therapeutic utility

“…Due to their capacity for placental formation, trophoblast EVs are also enriched in a myriad of pro-angiogenic molecules, including human miR-1290 [195] and porcine miR-126-5P, miR-296-5P, miR-16, and miR-17-5P [196]. In fact, trophoblast EVs with dysregulated expression of angio-genic molecules (e.g., miR-302a via direct targeting of VEGFA [197]) can significantly repress angiogenesis, resulting in placenta-related pathologies such as preeclampsia [197], highlighting EV composition as a critical regulator of pregnancy outcomes. Such differences in how composition of EVs in these examples are influenced by specific conditions of embryo or uterus remain to be determined.…”

Placental Exosomes as Biomarkers for Maternal Diseases: Current Advances in Isolation, Characterization, and Detection

“…Exosomes released by the blastocyst may affect gene expression and receptivity of endometrial cells, thereby facilitating and regulating the implantation . The role of exosomes in pregnancy has been recognized as a regulator of several processes, such as maternal immune response and metabolic modulations. − During pregnancy, the release of exosomes is influenced by several cellular microenvironment factors such as hypoxia or high glucose concentration. − Placenta-derived exosomes have been found to regulate the migration and invasion of recipient cells, playing a vital role in cell-to-cell communication and potentially contributing to the placentation and development of maternal–fetal vascular exchange. − …”