Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia.
Reprod Sci. 2013 Mar;20(3):308-17. doi: 10.1177/1933719112453507. Epub 2012 Aug 17.
MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women. We found hsa-miR-30b and hsa-miR-30d to be significantly upregulated, and hsa-miR-494 and hsa-miR-923 to be downregulated in receptive endometrium. Three algorithms (miRanda, PicTar, and TargetScan) were used for target gene prediction. Functional analyses of the targets using Ingenuity Pathways Analysis and The Database for Annotation, Visualization and Integrated Discovery indicated roles in transcription, cell proliferation and apoptosis, and significant involvement in several relevant pathways, such as axon guidance, Wnt/β-catenin, ERK/MAPK, transforming growth factor β (TGF-β), p53 and leukocyte extravasation. Comparison of predicted miRNA target genes and our previous messenger RNA microarray data resulted in a list of 12 genes, including CAST, CFTR, FGFR2, and LIF that could serve as a panel of genes important for endometrial receptivity. In conclusion, we suggest that a subset of miRNAs and their target genes may play important roles in endometrial receptivity.
微小 RNA(miRNA)作为基因表达的重要表观遗传转录后调控因子。我们旨在通过分析生育期女性子宫内膜的 miRNA 特征,来更好地理解子宫内膜容受性的复杂基因表达调控。我们对来自健康生育期女性的具有容受性(LH+7,n=4)和非容受性(LH+2,n=5)的子宫内膜进行 miRNA 特征分析。我们发现 hsa-miR-30b 和 hsa-miR-30d 显著上调,hsa-miR-494 和 hsa-miR-923 下调。使用 miRanda、PicTar 和 TargetScan 三种算法进行靶基因预测。使用 IPA 和 DAVID 对靶基因进行功能分析表明,这些靶基因参与转录、细胞增殖和凋亡,并且显著参与几个相关通路,如轴突导向、Wnt/β-catenin、ERK/MAPK、转化生长因子β(TGF-β)、p53 和白细胞渗出。预测的 miRNA 靶基因与我们之前的信使 RNA 微阵列数据的比较产生了 12 个基因的列表,包括 CAST、CFTR、FGFR2 和 LIF,它们可以作为一组对子宫内膜容受性重要的基因。总之,我们认为一组 miRNA 和它们的靶基因可能在子宫内膜容受性中发挥重要作用。