Hsa-miR-222 Is Involved in Differentiation of Endometrial Stromal Cells in Vitro
Hsa-miR-222 Is Involved in Differentiation of Endometrial Stromal Cells in Vitro
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Hsa-miR-222参与子宫内膜基质细胞的体外分化
DOI：
10.1210/en.2008-1629
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Hanwang
中科院分区：
文献类型：
--
作者：
Qian, Kun;Hu, Linli;Zhang, Hanwang
蜕膜化是胚胎着床的关键步骤，其特征在于子宫内膜基质细胞（ESCs）分化为蜕膜细胞。由于miRNA是决定细胞命运的重要因素，因此本研究采用微阵列技术对体外培养的ESCs在蜕膜化过程中的miRNA表达进行了分析。微阵列的显著性分析显示，49个miRNA基因在未诱导的ESCs和诱导的ESCs之间差异表达（>2倍），错误发现率为0。定量PCR检测hsa-miR-222、221、143、101、30 d、30 c、181 b、27 b、29 b、507和23 a的表达差异（P <0. 05）。基于microRNA（miRNA）和mRNA表达差异以及预测的miRNA靶基因，构建了一个miRNA调控ESCs分化的生物信息学模型。下调has-miR-222表达可使ESCs分化过程中S期细胞数减少（P < 0.05）。has-miR-222反义寡核苷酸可通过靶向CDKN 1C/p57 kip 2 mRNA的3'非翻译区，提高报告基因的表达，并提高CDKN 1C/p57 kip 2蛋白水平（P < 0.05）。总之，我们的研究结果表明，一个小分子RNA的子集在胚胎干细胞蜕膜化过程中的基因重编程中发挥了关键作用，hsa-miR-222通过调节胚胎干细胞最终退出细胞周期参与胚胎干细胞分化。（内分泌学150：4734-4743，2009）
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. (Endocrinology 150: 4734-4743, 2009)