Mmu-microRNA-200a Overexpression Leads to Implantation Defect by Targeting Phosphatase and Tensin Homolog in Mouse Uterus
Mmu-microRNA-200a Overexpression Leads to Implantation Defect by Targeting Phosphatase and Tensin Homolog in Mouse Uterus
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Mmu-microRNA-200a 过表达通过靶向小鼠子宫中的磷酸酶和张力蛋白同源物导致植入缺陷
DOI：
10.1177/1933719113488453
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发表时间：
2013-12-01
影响因子：
2.9
通讯作者：
Wang, Ying-Xiong
中科院分区：
文献类型：
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作者：
Shen, Lian-Ju;He, Jun-Lin;Wang, Ying-Xiong
成功的小鼠胚胎植入需要接受性子宫和激活的胚泡。大量的基因、细胞因子和其他因素参与了这一过程。microRNAs（miRNAs）调控着许多基因的表达，先前的研究已经探讨了miRNAs表达与胚胎着床的关系。在本研究中，我们发现mmu-microRNA-200 a（mmu-miR-200 a）在小鼠子宫着床过程中以时空方式表达，并通过生物信息学分析发现磷酸酶和张力蛋白同源物（PTEN）、SON和程序性细胞死亡4（Pdcd 4）是mmu-miR-200 a的靶基因。体外功能获得和丧失实验证实，细胞增殖和凋亡的关键基因PTEN是mmu-miR-200 a的靶基因。我们的实验还表明，用mmu-miR-200 a慢病毒注射子宫角导致植入率降低。总之，我们的研究结果表明mmu-miR-200 a通过调节PTEN蛋白表达影响胚胎着床。因此，阐明子宫miRNAs的生理功能将有助于阐明胚胎着床过程，甚至可能有助于治疗不孕症和发明新的避孕药。
Successful mouse embryo implantation requires a receptive uterus and an activated blastocyst. A large number of genes, cytokines, and other factors are involved in the process. MicroRNAs (miRNAs) regulate the expression of many genes, and previous studies have investigated the relationship between miRNA expression and embryo implantation. In this study, we show that mmu-microRNA-200a (mmu-miR-200a) is expressed in a spatiatemporal manner during implantation in mouse uterus and found that phosphatase and tensin homolog (PTEN),SON, and programmed cell death 4 (Pdcd4) are the target genes of mmu-miR-200a by bioinformatics analysis. In vitro gain and loss of function experiments confirm thatPTEN, a critical gene for cell proliferation and apoptosis, is the target gene of mmu-miR-200a. Our experiments also show that injection of the uterine horn with mmu-miR-200a lentivirus leads to a decreased implantation rate. Collectively, our results suggest that mmu-miR-200a affects embryo implantation by regulating PTEN protein expression. Thus, clarifying the physiological functions of uterine miRNAs will help to elucidate the embryo implantation process and may even contribute to curing infertility and inventing new contraceptives.