MicroRNA regulation of transthyretin in trophoblast biofunction and preeclampsia
MicroRNA regulation of transthyretin in trophoblast biofunction and preeclampsia
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MicroRNA 调控甲状腺素运载蛋白在滋养层生物功能和先兆子痫中的作用
DOI：
10.1016/j.abb.2019.108129
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发表时间：
2019-11-15
影响因子：
3.9
通讯作者：
Zhang, Zhenyu
中科院分区：
文献类型：
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作者：
Cao, Guangming;Cui, Ran;Zhang, Zhenyu
子痫前期(PE)是孕产妇、胎儿和新生儿死亡的主要原因，影响大约2-7%的妊娠。反式甲状腺激素(TTR)在PE孕妇血清和胎盘中表达下调。我们的生物信息学分析表明，TTR是miR-200a-3p和miR-141-3p的预测靶标。本研究的目的是确定miR-200a-3p和miR-141-3p是否通过靶向胎盘滋养层细胞中的TTR参与子痫前期的发生。在人PE胎盘中，随着miR-141-3p和200A-3p的高表达，TTR的转录和蛋白水平显著降低。我们发现miR-200A-3p和miR-141-3p通过直接与TTR3‘端非编码区结合来抑制TTR的表达，而这种作用被microRNA结合位点的突变所逆转。在子痫前期患者血浆中，TTR水平显著下调。在JEG3细胞中，用双荧光素酶分析证实TTR是miR-200a-3p和miR-141-3p的直接靶点。Transwell插入侵袭实验表明，TTR介导了miR-200A-3p和miR-141-3p对JEG3细胞的侵袭抑制作用。这些数据为了解miR-141-3p和miR-200a-3p在滋养层功能障碍和PE发育过程中调节TTR的生理作用提供了新的视角。
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.