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生物信息学分析反复植入失败妊娠疾病的调控因子及潜在治疗药物

Identification of Regulation Factors and Potential Therapeutic Drugs in Pregnancy Disease Recurrent Implantation Failure Based on Bioinformatics

  • 摘要: 子宫内膜容受性在胚胎着床及正常妊娠维持中具有关键作用,其损伤或异常将导致反复植入失败(recurrent implantation failure, RIF)妊娠疾病。本研究利用生物信息学方法筛选了RIF患者子宫内膜容受性不足的潜在调控靶标及治疗药物。从GEO数据库中检索并下载了目前已有的RIF的窗口期子宫内膜数据。利用RobustRankAggreg从6组mRNA表达数据集的246个样本中共筛选到95个差异表达mRNA,并发现EGR1、FOS等10个节点基因是RIF的潜在调控因子,且炎症反应调控、对缺血的响应等通路参与RIF进展。从2组microRNA表达数据集的85个样本中筛选到3个差异表达microRNA,进一步通过microRNA-mRNA调控网络分析发现miR-449b-5p、miR-186-5p可能靶向调控多个差异mRNA进而参与RIF。最后,通过CMap药物分析发现抗炎药物氨普立糖(amiprilose)和氨苯砜(dapsone)可能是RIF治疗的候选药物。本研究为解析子宫内膜容受性异常机制及提高辅助生殖技术成功率提供了线索。

     

    Abstract: Endometrial receptivity plays a key role in embryo implantation and normal pregnancy maintenance. Its injury or abnormality will lead to pregnancy diseases such as recurrent implantation failure(RIF). In this study, bioinformatics methods were used to identify the potential regulatory targets and therapeutic drugs for impaired endometrial receptivity in patients with RIF. The currently existing datasets of women endometrium in window period with/without RIF were retrieved and downloaded from GEO database. Total of 95 differentially expressed mRNAs were identified from 246 samples in 6 groups of datasets by RobustRankAggreg method. It was found that 10 hub genes such as EGR1 and FOS are potential regulators of RIF, and pathways such as regulation of inflammatory response, response to ischemia are involved RIF progress. 3 differentially expressed microRNAs were identified from 85 samples in 2 groups of datasets. Further analysis of mRNA-microRNA regulatory network revealed that miR-449-5 p and miR-186-5 p may participated in RIF by regulate multiple differentially expressed mRNAs. Finally, the anti-inflammatory drugs amprilose and dapsone may be drug candidates for RIF therapy through the drug analysis of CMap. This study provides clues for understanding the mechanism of endometrial receptivity and improving the success rate of assisted reproductive technology.

     

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