Zhang Xin-Xian, Zhang Zhi-Chao, Liu Yu-Shan, Zhou Li, Hu Yu-Qin, Zhang Cai-Hong, Song Wen-Hui, Wu Xiao-Hua
Reproductive Medicine Center, The Fourth Hospital of Shijiazhuang, Hebei Medical University, 206 East Zhongshan Road, Shijiazhuang, 050011, Hebei, China.
Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050011, Hebei, China.
Biochem Genet. 2024 Jun 10. doi: 10.1007/s10528-024-10857-8.
Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.
相关研究指出，杀伤细胞免疫球蛋白样受体2DL4（KIR2DL4）与早期妊娠的血管重塑有关，可能在免疫中发挥重要作用。本研究从基因表达综合数据库（GEO）中提取复发性植入失败（RIF）相关的GSE58144数据集。首先，进行免疫微环境分析以分析KIR2DL4在RIF中的发病机制。然后，进行基因集富集分析（GSEA）以研究KIR2DL4的功能。此外，构建TF-mRNA-miRNA和共表达网络以揭示KIR2DL4的潜在调控机制。此外，获得与KIR2DL4相关且在RIF中差异表达的基因并将其定义为关键基因，并进一步探索这些基因的功能。KIR2DL4可用于RIF的临床诊断，且与RIF中免疫微环境的变化相关。从功能角度来看，KIR2DL4与补体和凝血级联反应、自然杀伤细胞介导的细胞毒性等有关。此外，用KIR2DL4、9个转录因子（TF）和29个微小RNA（miRNA）构建了TF-mRNA-miRNA调控网络。此外，筛选出KIR2DL4、ACSM1、IL2RB和PTPN11作为关键基因，它们与免疫相关功能有关。本研究深入分析了KIR2DL4的功能及其在RIF中的作用，我们发现信号转导和转录激活因子1（STAT1）可能通过INF-γ/JAK2/STAT1信号通路上调KIR2DL4。此外，黄体中期子宫内膜中KIR2DL4的过表达可能通过影响胚胎植入微环境来影响胚胎植入，这可能有助于加深对RIF分子机制的理解。
