Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania 15213, USA.
Biol Reprod. 2013 Aug 1;89(2):25. doi: 10.1095/biolreprod.113.110049. Print 2013 Aug.
Placental hypoperfusion causes cellular hypoxia and is associated with fetal growth restriction and preeclampsia. In response to hypoxia, the repertoire of genes expressed in placental trophoblasts changes, which influences key cellular processes such as differentiation and fusion. Diverse miRNAs were recently found to modulate the cellular response to hypoxia. Here we show that miR-424, which was previously shown to be upregulated by hypoxia in nontrophoblastic cell types, is uniquely downregulated in primary human trophoblasts by hypoxia or chemicals known to hinder cell differentiation. We also identify FGFR1 as a direct target of miR-424 in human trophoblasts. This effect is unique to miR-424 and is not seen with other members of this miRNA family that are expressed in trophoblasts, such as miR-15 and miR-16. Our findings establish a unique role for miR-424 during differentiation of human trophoblasts.
胎盘灌注不足会导致细胞缺氧，与胎儿生长受限和子痫前期有关。为了应对缺氧，胎盘滋养细胞中表达的基因谱发生变化，这影响了关键的细胞过程，如分化和融合。最近发现多种 miRNA 可以调节细胞对缺氧的反应。在这里，我们表明，miR-424 先前被证明在非滋养细胞类型中由缺氧上调，在原发性人滋养细胞中由缺氧或已知阻碍细胞分化的化学物质特异性地下调。我们还确定 FGFR1 是人类滋养细胞中 miR-424 的直接靶标。这种作用是 miR-424 所特有的，在其他表达于滋养细胞的 miRNA 家族成员中没有发现，如 miR-15 和 miR-16。我们的发现确立了 miR-424 在人滋养细胞分化过程中的独特作用。
