miR455 is linked to hypoxia signaling and is deregulated in preeclampsia.
miR455 is linked to hypoxia signaling and is deregulated in preeclampsia.
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DOI：
10.1038/cddis.2014.368
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发表时间：
2014-09-04
影响因子：
9
通讯作者：
Bühler M
中科院分区：
文献类型：
--
作者：
Lalevée S;Lapaire O;Bühler M
先兆子痫是一种严重的妊娠相关疾病，是全球孕产妇和胎儿死亡的主要原因。因此，早期识别先兆子痫风险增加的患者是产科最重要的目标之一。在这里，我们确定了两个相关的人类microRNA作为潜在的生物标志物来检测高危妊娠。我们证明了miR 455 - 3 P和miR 455 - 5 P在先兆子痫患者的胎盘中显著下调，而其他胎盘特异性microRNA则不受影响。microRNA靶标预测和验证揭示了miR 455 - 3 P与缺氧信号传导的潜在联系。结合我们观察到的miR 455 - 3 P和miR 455 - 5 P的表达水平在滋养层分化过程中上调，我们的结果表明，miR 455 - 3 P抑制缺氧反应，否则可能会阻止细胞滋养层从合胞体滋养层分化的模型。总之，我们的工作揭示了先兆子痫中异常的缺氧信号传导，这可以通过miR 455的表达失调来解释。由于在循环血液中发现了miR 455，因此开发能够早期诊断先兆子痫的非侵入性产前检测是可能的。
Preeclampsia is a severe pregnancy-related disorder and a leading cause of maternal and fetal mortality worldwide. Early identification of patients with an increased risk for preeclampsia is thus one of the most important goals in obstetrics. Here we identify two related human microRNAs as potential biomarkers to detect at-risk pregnancies. We demonstrate that miR455-3P and miR455-5P are significantly downregulated in placentas from preeclampsia patients, whereas other placenta-specific microRNAs remain unaffected. microRNA target prediction and validation revealed a potential link of miR455-3P to hypoxia signaling. Together with our observation that expression levels of miR455-3P and miR455-5P are upregulated during trophoblast differentiation, our results suggest a model in which miR455-3P represses a hypoxia response that might otherwise prevent cytotrophoblasts from syncytiotrophoblast differentiation. In summary, our work reveals aberrant hypoxia signaling in preeclampsia that can be explained by deregulated expression of miR455. As miR455 has been found in circulating blood, the development of noninvasive prenatal tests enabling early diagnosis of preeclampsia may be possible.