MicroRNA regulation of transthyretin in trophoblast biofunction and preeclampsia

Preeclampsia (PE) is the major cause of maternal, fetal and neonatal mortality affecting approximately 2-7% of pregnancies. Transthyretin (TTR) is down-regulated in PE pregnancies serum and placenta. Our bioinformatic analysis showed that TTR is a predicted target for miR-200a-3p and miR-141-3p. The aim of this study was to determine whether miR-200a-3p and miR-141-3p are involved in preeclampsia through its targeting of TTR in human placental trophoblasts. In human PE placenta, TTR transcript and protein levels were significantly lower associated with high expression of miR-141-3p and 200a-3p. We found that miR-200a-3p and miR-141-3p inhibited TTR expression by directly binding to the 3'UTR of TTR, which is reversed by mutation in the microRNA binding site. In preeclamptic plasm, TTR levels were significantly downregulated. TTR was validated as a direct target of miR-200a-3p and miR-141-3p using dual luciferase assays in JEG3 cells. Transwell insert invasion assays showed that TTR mediated the invasion-inhibitory effect of miR-200a-3p and miR-141-3p in JEG3 cells. These data provides new insight into physiological role of miR-141-3p and miR-200a-3p in regulating TTR during trophoblast dysfunction and PE development.