Hsa-miR-222 Is Involved in Differentiation of Endometrial Stromal Cells in Vitro

Abstract

Decidualization is a critical step during embryo implantation and characterized by the differentiation of endometrial stromal cells (ESCs) into decidual cells. Because miRNAs are important determinants of cellular fate specification, in this study, the miRNA expression in ESCs during in vitro decidualization was profiled by using a microarray. Significance analysis of microarrays revealed that 49 miRNA genes were differently (>2-fold) expressed between the noninduced ESCs and induced ESCs with a false discovery rate of 0. The expression variance of hsa-miR-222, 221, 143, 101, 30d, 30c, 181b, 27b, 29b, 507, and 23a was validated by using quantitative PCR (P < 0.05). Based on microRNA (miRNA) and mRNA expression variance and predicted target genes of miRNAs, a bioinformatic model of miRNAs controlling ESCs differentiation was formulated. Finally, we proved that down-regulation of has-miR-222 could decrease the number of cells in S phase during ESCs differentiation (P < 0.05). Antisense oligonucleotides of has-miR-222 could increase reporter gene expression by targeting the 3' untranslated regions of CDKN1C/p57kip2 mRNAs as well as increase CDKN1C/p57kip2 protein levels (P < 0.05). In conclusion, our results suggest that a subset of miRNAs play a key role in gene reprogramming during ESCs decidualization and that hsa-miR-222 participates in ESC differentiation by regulating ESCs terminally withdrawing from the cell cycle.

MicroRNAs, immune cells and pregnancy

“…72,73 Additionally, a subset of miRNAs (hsa-miR-222, 221, 181b, 27b, 29b, 507, 143, 101, 30d, 30c and 23a) participates in gene reprogramming during endometrial stromal cell (ESC) decidualization in vitro and hsa-miR-222 was found to play a key role in differentiation of ESCs by regulating their terminal withdrawal from the cell cycle. 74 In our laboratory, studies on spontaneous fetal loss in pigs have provided evidence of selective miRNA expression in endometrial lymphocytes (unpublished data). Our research shows that miRNAs reported to be involved in immune cell development and angiogenesis (miR-150, miR-17-5P, miR-18a, miR-19a and miR-296-5P) differ significantly between endometrial lymphocytes isolated by laser capture microdissection from conceptus attachment sites associated with growth arrest compared with healthy embryos (unpublished data).…”

The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

“…The expression of miRNAs has also been studied in human endometrial stromal cells that were decidualised in culture for 4 days. Interestingly, out of 49 miRNAs regulated twofold or more, two-thirds were reported to be downregulated in decidualising cells (Qian et al 2009). However, these results should be interpreted with caution as decidualising endometrial cells acquire a highly secretory phenotype, suggesting that miRNAs may be produced primarily for export.…”

Macro-management of microRNAs in cell cycle progression of tumor cells and its implications in anti-cancer therapy

“…The CDK inhibitor p21 is targeted by miR-17-92 and miR106b/93 [22,25] in addition to many other miRNAs [50,51] . The p27 and p57 proteins are regulated by miR-221/222 [52,53] and miR92b [54] . The INK family member p16 is regulated by miR-24 [55] .…”