Altered Expression of GABPB1-IT1 and SLC9A3-AS1 Long Non-Coding RNAs in Recurrent Implantation Failure

Abstract

Background: Recurrent implantation failure (RIF) impairs assisted reproductive technology (ART) success, though its mechanisms remain unclear. Studies have implicated altered miRNA expression in the plasma and endometrium of patients with RIF. In this study, long non-coding RNA (lncRNA) expression in plasma was investigated, using RIF-specific lncRNA-miRNA-mRNA network as guide.

Methods: This study included 30 women with RIF and 30 age-matched controls (Not RIF). RIF miRNA RNA-seq data (GSE108966) was downloaded from the Gene Expression Omnibus (GEO) database and used to identify differentially expressed miRNAs. Next, miRNet 2.0 database was used to integrate the latest miRNA-mRNA interactions; also, the linkages between lncRNA and miRNA were identified and the networks created. Plasma samples were collected from participants during the implantation window. Cell-free RNA was extracted from 500 µl of plasma using the TRIzol method, and statistical analyses were performed using Prism version 8.0.

Results: Based on a lncRNA-miRNA-mRNA network analysis, two lncRNAs, including GABPB1-IT1 and SLC9A3-AS1, were selected for expression analysis in plasma. Notably, GABPB1-IT1 and SLC9A3-AS1 were significantly downregulated in RIF samples compared to controls.

Conclusion: Our findings show that GABPB1-IT1 and SLC9A3-AS1 are significantly downregulated in the plasma of women with recurrent implantation failure. These findings suggest their potential involvement in RIF and warrant further studies to elucidate their biological functions and evaluate their utility as non-invasive biomarkers.