Xie Lan, Mouillet Jean-Francois, Chu Tianjiao, Parks W Tony, Sadovsky Elena, Knöfler Martin, Sadovsky Yoel
Magee-Womens Research Institute (L.X., J.-F.M., T.C., W.T.P., E.S., Y.S.), Department of OBGYN and Reproductive Sciences, University of Pittsburgh, Pennsylvania 15213; Medical Systems Biology Research Center (L.X.), Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing 100084 China; Department of Obstetrics and Fetal-Maternal Medicine (M.K.), Reproductive Biology Unit, Medical University of Vienna, Vienna, A-1090 Austria; and Department of Microbiology and Molecular Genetics (Y.S.), University of Pittsburgh, Pennsylvania 15213.
Endocrinology. 2014 Dec;155(12):4975-85. doi: 10.1210/en.2014-1501. Epub 2014 Sep 11.
Early in pregnancy, trophoblast invasion into the decidua and inner myometrium is essential for establishment of proper implantation, maternal-fetal exchange, and immunological tolerance of the feto-placental allograft. Unlike villous trophoblasts (VTs), extravillous trophoblasts (EVTs) are unique in their capacity to invade the maternal decidua and myometrium. The largest human microRNA (miRNA) gene cluster, the chromosome 19 miRNA cluster (C19MC), is expressed almost exclusively in the placenta and, rarely, in certain tumors and undifferentiated cells. In the work reported here, we found that the expression of C19MC miRNAs is higher in VTs than in EVTs. Using a bacterial artificial chromosome (BAC)-mediated overexpression of C19MC miRNAs in an EVT-derived cell line, which does not naturally express these miRNAs, we found that C19MC miRNAs selectively attenuate cell migration without affecting cell proliferation or apoptosis. A microarray analysis revealed that C19MC miRNAs regulate target transcripts related to cellular movement. Our data also implicated a specific C19MC member, miR-519d, indirectly regulating the EVT invasive phenotype by targeting CXCL6, NR4A2 and FOXL2 transcripts through a 3'UTR miRNA-responsive element. Together, our data suggest a role for C19MC miRNAs in modulating the migration of EVTs.
在妊娠早期，滋养层细胞侵入蜕膜和子宫肌层内层对于建立适当的着床、母胎交换以及对胎儿 - 胎盘同种异体移植物的免疫耐受至关重要。与绒毛滋养层细胞（VTs）不同，绒毛外滋养层细胞（EVTs）具有侵入母体蜕膜和子宫肌层的独特能力。人类最大的微小RNA（miRNA）基因簇，即19号染色体miRNA簇（C19MC），几乎仅在胎盘中表达，在某些肿瘤和未分化细胞中很少表达。在本文报道的研究中，我们发现C19MC miRNAs在VTs中的表达高于EVTs。在一个不自然表达这些miRNAs的EVT来源细胞系中，利用细菌人工染色体（BAC）介导C19MC miRNAs的过表达，我们发现C19MC miRNAs选择性地减弱细胞迁移，而不影响细胞增殖或凋亡。微阵列分析显示，C19MC miRNAs调节与细胞运动相关的靶转录本。我们的数据还表明，特定的C19MC成员miR - 519d通过3'UTR miRNA反应元件靶向CXCL6、NR4A2和FOXL2转录本，间接调节EVT的侵袭表型。总之，我们的数据表明C19MC miRNAs在调节EVTs迁移中发挥作用。
