Recently, the etiopathogenesis of preeclampsia (PE) has been developed from the perspective of circular RNA, microRNA and their crosstalk in placental oxidative stress. Real-time quantitative PCR and western blotting detected… Click to show full abstract
Recently, the etiopathogenesis of preeclampsia (PE) has been developed from the perspective of circular RNA, microRNA and their crosstalk in placental oxidative stress. Real-time quantitative PCR and western blotting detected expression of circular RNA-fibronectin 1 (circFN1; ID hsa_circ_0058152), microRNA (miR)-19a/b-3p and activating transcription factor 2 (ATF2). Receiver operating characteristic (ROC) curve analyzed the predictive value of circFN1. Oxidative stress, apoptosis, proliferation, and migration were measured using superoxide dismutase (SOD) and malonaldehyde (MDA) assay kits, Annexin V/Prodium iodide and western blotting methods, MTS and EdU assays, and scratch wound assay, respectively. Target relationships were retrieved by miRNA target prediction software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Expression of circFN1 was upregulated in the serum of PE pregnancies, and the area under the ROC curve of serum circFN1 was 0.7826 (95% confidence interval: 0.6495-0.9157; sensitivity 86.96%; specificity 56%). Functionally, its upregulation decreased SOD activity, cell viability, EdU incorporation, migration rate, and Bcl-2 expression in human trophoblast HTR-8/SV-neo cells, but meanwhile increased MDA level, apoptosis rate, and Bax and cleaved-caspase3 expression. Moreover, its downregulation played the opposite effects in HTR-8/SV-neo cells. Mechanistically, circFN1 functioned as "miRNA sponge" for miR-19a/b-3p and modulated the latter's target gene ATF2. There were feedback effects of miR-19a/b-3p restorations and ATF2 depletion on circFN1 actions in HTR-8/SV-neo cells. Oxidative injury-mediated placental trophoblast dysfunction in PE was through competing endogenous RNA (ceRNA) mechanism of CircFN1-miR-19a/b-3p-ATF2 axes.
               
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