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

Abstract

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. 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. 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. 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.