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Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia.
Cell Death Discovery ( IF 6.1 ) Pub Date : 2020-05-13 , DOI: 10.1038/s41420-020-0269-0
Qinghua Li 1 , Yangyang Han 2, 3 , Peng Xu 4 , Lingxuan Yin 2, 3 , Yanru Si 2, 3 , Cuijuan Zhang 5 , Yuhan Meng 6 , Weiguo Feng 2, 3 , Zhifang Pan 2, 3 , Zhiqin Gao 2, 3 , Jie Li 5 , Weiwei Yang 2, 3
Affiliation  

Preeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5-8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated (p < 0.01) in patients who later developed PE. Circulating hsa-miR-125b was aberrantly upregulated in early pregnancy and significantly reduced after delivery in preeclampsia. We then investigated the underlying molecular mechanisms between miR-125b and PE in vitro. We found that upregulated miR-125b can target KCNA1 to inhibit trophoblast invasion in human trophoblast cells. Moreover, overexpression of miR-125b in HUVECs impaired endothelial cell function through GPC1. The findings indicated that upregulated miR-125b leads to impaired placentation, and an increased risk of preeclampsia, Our studies provide novel insights into the underlying mechanisms on the association of miR-125b in early pregnancy and risk of PE, miR-125b might be a more specific predictive marker and a safe therapeutic target for treating patients with PE.

中文翻译:


升高的 microRNA-125b 会抑制先兆子痫患者的细胞滋养层侵袭并损害内皮细胞功能。



先兆子痫 (PE) 是一种危及生命的人类妊娠疾病,影响 5-8% 的妊娠。目前,早泄仍然是一种难以捉摸的复杂且异质的医学状况,没有发现这种严重妊娠并发症的早期标志或症状。在这里,我们分析了与先兆子痫相关的血浆 miRNA 表达模式,发现后来发生 PE 的患者中有 16 个 miRNA 失调 (p < 0.01)。循环 hsa-miR-125b 在妊娠早期异常上调,在先兆子痫中分娩后显着降低。然后我们在体外研究了 miR-125b 和 PE 之间的潜在分子机制。我们发现上调的 miR-125b 可以靶向 KCNA1 抑制人滋养层细胞的滋养层侵袭。此外,HUVEC 中 miR-125b 的过度表达通过 GPC1 损害内皮细胞功能。研究结果表明,上调的 miR-125b 会导致胎盘受损,并增加先兆子痫的风险,我们的研究为 miR-125b 在妊娠早期与 PE 风险之间的关联提供了新的见解,miR-125b 可能是一个更具体的预测标记和治疗PE患者的安全治疗靶点。
更新日期:2020-05-13
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