Abstract
BackgroundThe 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.MethodsWeighted 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.ResultsA 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.ConclusionsWe 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.
Highlights
The mechanism of recurrent implantation failure (RIF) is unclear at present and poor endometrial receptivity may be one of the leading reasons
Identification of differentially expressed messenger RNA (mRNA) (DEMs) and long non-coding RNA (lncRNA) (DELs) The limma package was used for identifying DEMs and Differentially expressed long non-coding RNAs (DELs) between the RIF samples and matched normal samples in GSE111974 [27]
A total of 17,596 genes were obtained for analysis, including 17,154 mRNAs and 442 lncRNAs
Summary
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. A significant proportion of couples would experience recurrent implantation failure (RIF), leading to great financial and psychological burden in these patients [4]. According to the latest criteria proposed by Coughlan et al [6], RIF refers to the failure to achieve clinical pregnancy after transfer of ≥ 4 morphologically good-quality embryos for ≥ 3 fresh or frozenthawed cycles in women less than 40 years old. Further studies are still urgently needed to elucidate the underlying mechanism, identify new prognostic biomarkers and develop potential therapeutic targets
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