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. 2013 Mar;20(3):308-17.
doi: 10.1177/1933719112453507. Epub 2012 Aug 17.

MicroRNAs miR-30b, miR-30d, and miR-494 regulate human endometrial receptivity

Signe Altmäe  1 , Jose A Martinez-Conejero, Francisco J Esteban, Maria Ruiz-Alonso, Anneli Stavreus-Evers, Jose A Horcajadas, Andres Salumets
Affiliations

MicroRNAs miR-30b, miR-30d, and miR-494 regulate human endometrial receptivity

Signe Altmäe et al. Reprod Sci. 2013 Mar.

Abstract

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.

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Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Heat map and cluster dendrograms of microRNA (miRNA) clusters differentially expressed between prereceptive (luteinizing hormone [LH] + 2) and receptive (LH + 7) endometrium. Upregulated miRNAs are marked in red and downregulated in green. The figure was done with the VSN normalized values of the 82 miRNAs with a RankProd raw P value <.05.
Figure 2.
Figure 2.
Venn diagram of the predicted target genes of miR-30b, miR-30d, miR-494, and miR-923. PicTar, miRanda, and TargetScan algorithms were used to create the common list of targets. Venn diagrams were obtained using the Venny interactive tool (http://bioinfogp.cnb.csic.es/tools/venny/index.html).
Figure 3.
Figure 3.
MicroRNA (miRNA) array validation by real-time polymerase chain reaction (PCR). Expression levels of miR-30b, miR-30d, miR-494, and miR-923 in receptive versus prereceptive endometrium in miRNA array analysis in comparison with real-time PCR analysis are presented.
See this image and copyright information in PMC

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