复发性植入失败(RIF)是一种复杂且鲜为人知的临床疾病,其特征是重复胚胎移植后无法受孕。子宫内膜容受性(ER)是植入的先决条件,和ER障碍与RIF相关。然而,关于RIF中ER的分子机制知之甚少。在本研究中,分析了有和没有RIF的患者的分泌期中子宫内膜的RNA测序数据,以探索参与RIF的潜在的长链非编码RNA(lncRNA)和信使RNA(mRNA)。分析揭示了213和1485差异表达的mRNA和lncRNA,分别为(倍数变化≥2和p<0.05)。基因本体论和京都百科全书的基因和基因组富集分析表明,这些基因主要参与与免疫或炎症相关的过程。5个关键基因(TTR,ALB,TF,法新社,和CFTR)和一个关键模块,包括14个枢纽基因(AFP,ALB,APOA1、APOA2、APOB、APOH,FABP1,FGA,FGG,GC,在蛋白质-蛋白质相互作用(PPI)网络中鉴定了ITH2,SERPIND1,TF和TTR)。5个关键基因用于进一步探索lncRNA-miRNA-mRNA调控网络。最后,通过CMap鉴定了基于14个hub基因的药物ML-193。ML-193治疗后,子宫内膜细胞增殖增加,中枢基因大部分被下调,ER标记HOXA10上调。这些结果提供了对lncRNAs和mRNAs的调节机制的见解,并表明ML-193通过增强ER作为RIF的治疗剂。
Recurrent implantation failure (RIF) is a complex and poorly understood clinical disorder characterized by failure to conceive after repeated embryo transfers. Endometrial receptivity (ER) is a prerequisite for implantation, and ER disorders are associated with RIF. However, little is known regarding the molecular mechanisms underlying ER in RIF. In the present study, RNA sequencing data from the mid-secretory endometrium of patients with and without RIF were analyzed to explore the potential long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in RIF. The analysis revealed 213 and 1485 differentially expressed mRNAs and lncRNAs, respectively (fold change ≥ 2 and p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these genes were mostly involved in processes related to immunity or inflammation. 5 key genes (TTR, ALB, TF, AFP, and CFTR) and a key module including 14 hub genes (AFP, ALB, APOA1, APOA2, APOB, APOH, FABP1, FGA, FGG, GC, ITIH2, SERPIND1, TF and TTR) were identified in the protein-protein interaction (PPI) network. The 5 key genes were used to further explore the lncRNA-miRNA-mRNA regulatory network. Finally, the drug ML-193 based on the 14 hub genes was identifed through the CMap. After ML-193 treatment, endometrial cell proliferation was increased, the hub genes were mostly down-regulated, and the ER marker HOXA10 was up-regulated. These results offer insights into the regulatory mechanisms of lncRNAs and mRNAs and suggest ML-193 as a therapeutic agent for RIF by enhancing ER.