Genome-wide analysis of long noncoding RNAs, microRNAs, and mRNAs forming a competing endogenous RNA network in repeated implantation failure.

Repeated implantation failure (RIF) was mainly due to poor endometrium receptivity. Long noncoding RNAs (lncRNAs) could regulate endometrium receptivity and act in competing endogenous RNA (ceRNA) theory. However, the regulatory mechanism of the lncRNA-miRNA-mRNA network in repeated implantation failure (RIF) is unclear. We obtained RIF-related expression profiles of lncRNAs, mRNAs, and miRNAs using mid-secretory endometrial tissue samples from 5 women with RIF and 5 controls by RNA-sequencing. Co-expression analysis revealed that three functional modules were enriched in immune response/inflammation process; two functional modules were enriched in metabolic/ biosynthetic process, and one functional module were enriched in cell cycle pathway. By adding the miRNA data, ceRNA regulatory relationship of each module was reconstructed. The ceRNA network of the whole differentially expressed RNAs revealed 10 hub lncRNAs. Among them, TRG-AS1, SIMM25, and NEAT1 were involved in the module1, module2, and module3, respectively; LNC00511 and SLC26A4-AS1 in the module4; H19 in the module5. The real-time polymerase chain reaction (RT-PCR) results of 15 randomly selected RNAs were consistent with our sequencing data. These can be used as novel potential biomarkers for RIF. Furthermore, they might be involved in endometrium receptivity by acting as ceRNA.