Small RNA sequencing reveals placenta-derived exosomal microRNAs associated with preeclampsia

Objective: Preeclampsia is one of the most important complications during pregnancy and the leading cause of maternal morbidity and mortality; however, the pathogenesis of preeclampsia remains partially misunderstood. The aim of this study was to identify placenta-derived exosomal microRNAs (miRNAs) involved in the preeclampsia process. Methods: Peripheral blood was collected from normal and preeclampsia pregnant women, and placenta-derived exosomes were extracted. Small RNA sequencing was performed to identify the exosomal miRNAs involved in preeclampsia. The function of a differentially expressed exosomal miRNA was verified. Results: The extracted exosomes presented round or ovallike structures with diameters of approximately 80 nm and could be recognized by antibodies against CD9, CD81, and placental alkaline phosphatase. A total of 1013 exosomal miRNAs were identified by small RNA sequencing, of which 946 were known miRNAs and 67 were novel miRNAs. Twenty-six miRNAs were identified as differentially expressed when comparing the data of the preeclampsia and normal groups. One of the differentially expressed miRNAs, hsa-miR-370–3p, which was upregulated in the preeclampsia group, was shown to bind to the 3’ untranslated region of C-X-C motif chemokine 12, a chemokine that plays important role during preeclampsia process. Moreover, functional analysis revealed that hsamiR-370–3p could inhibit proliferation, migration, and invasion while promoting apoptosis of HTR-8/SVneo cells. Conclusion: A total of 1013 placenta-derived exosomal miRNAs were identified by small RNA sequencing, of which 26 were differentially expressed. The function of one differentially expressed miRNA (hsa-miR-370–3p) was verified. Our results provide new perspectives on the pathogenesis of preeclampsia and potential biomarkers for preeclampsia diagnosis.