Reproductive Medical Center, Jiangxi Provincial Maternal and Child Health Hospital, 330006, Nanchang, China.
Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
Reprod Biol Endocrinol. 2021 Jul 9;19(1):108. doi: 10.1186/s12958-021-00778-1.
The mechanism of recurrent implantation failure (RIF) is unclear at present and poor endometrial receptivity may be one of the leading reasons. This study aims to construct a competing endogenous RNA (ceRNA) network and identify potential hub genes underlying the development of RIF.
Weighted gene co-expression network analysis was performed based on differentially expressed mRNAs (DEMs) and lncRNAs (DELs) from the GSE111974 dataset. Functional enrichment analyses of gene modules were conducted using Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway. A lncRNA-miRNA-mRNA ceRNA regulatory network was constructed according to predictive interaction derived from the LncRNADisease, miRTarBase, miRDB and TargetScan databases. Topological analysis determined the key genes with the highest centroid and their expressions were further verified using public datasets and quantitative real-time polymerase chain reaction.
A total of 1500 DEMs and 3 DELs were significantly up-regulated, whereas 1022 DEMs and 4 DELs were significantly down-regulated in the RIF group compared with the control group. Six functional co-expression modules were enriched in various biological processes, such as cell adhesion, regulation of cell motility and cellular response to vascular endothelial growth factor stimulus. Five hub genes were identified in the ceRNA network, of which GJA1 was down-regulated whereas TET2, MAP2K6, LRRC1 and TRPM6 were up-regulated in RIF endometrium.
We constructed a lncRNA-associated ceRNA network and identified five novel hub genes in RIF. This finding could be helpful to understand the molecular mechanism for RIF pathogenesis, and may provide novel insights for its early diagnosis and treatment.
目前复发性植入失败（RIF）的机制尚不清楚，而子宫内膜容受性差可能是主要原因之一。本研究旨在构建竞争性内源 RNA（ceRNA）网络，并确定与 RIF 发展相关的潜在关键基因。
基于 GSE111974 数据集的差异表达 mRNA（DEM）和长非编码 RNA（DEL）进行加权基因共表达网络分析。使用基因本体分类和京都基因与基因组百科全书通路对基因模块的功能富集分析。根据 LncRNADisease、miRTarBase、miRDB 和 TargetScan 数据库预测的相互作用，构建 lncRNA-miRNA-mRNA ceRNA 调控网络。拓扑分析确定了具有最高质心的关键基因，并使用公共数据集和实时定量聚合酶链反应进一步验证其表达。
与对照组相比，RIF 组中共有 1500 个 DEM 和 3 个 DEL 明显上调，而 1022 个 DEM 和 4 个 DEL 明显下调。在不同的生物学过程中，如细胞黏附、细胞运动调节和细胞对血管内皮生长因子刺激的反应，共富集了 6 个功能共表达模块。ceRNA 网络中确定了 5 个关键基因，其中 GJA1 下调，而 TET2、MAP2K6、LRRC1 和 TRPM6 在 RIF 子宫内膜中上调。
我们构建了一个 lncRNA 相关的 ceRNA 网络，并在 RIF 中鉴定了 5 个新的关键基因。这一发现有助于理解 RIF 发病机制的分子机制，并为其早期诊断和治疗提供新的思路。
