Identification Of Key CeRNA Regulation Network In Endometrium Of Rif Patients During Window Of Implantation

Background: Several studies recently have proposed that noncoding RNAs and coding RNAs are involved in embryo implantation by competing endogenous RNA(ceRNA)mechanisms(ceRNA)mechanism.However,the research is at the incipient stages and their functional mechanisms in RIF are not yet clear.Objective:The aim of this study is to identify for richer and more accurate whole transcriptional expression profiles in RIF and to analyze the potential regulatory mechanisms,exploring the potential regulatory functions and mechanisms that exist between nc RNA and m RNA.New insights into the pathogenesis of RIF from an epigenetic perspective.Methods: Whole transcriptome sequencing screening for differentially expressed nc RNAs and m RNAs(DEGs)in endometrial tissue during Window of implantation(WOI)in theRIF group(n=8)and control group(n=3).Transcription factor annotation and enrichment of m RNAs in the ceRNA regulatory network(ceRNA-m RNA).Enrichment analysis and protein-protein interaction(PPI)analysis were performed on ceRNA-m RNA and DEGs,respectively,and hub genes were screened using MCODE and cyto Hubba plug-ins.Results: A total of 270 m RNAs,67 micro RNAs,679 lnc RNAs,and106 circ RNAs are differentially expressed in theRIF patients.KEGG and Reactom pathway Enrichment analysis indicated that DEGs in RIF are enriched in immune function and signaling.GO analysis showed that most of the DEGs were located in the plasma membrane,which are similar to the results of ceRNA enrichment analysis.Comparing the Hub genes of ceRNA-m RNA and DEGs,we found that they have the same 5Hub genes,which contain BMP7,SOX2 and SIX1,and these three genes together with FOXC1 form a subnet in ceRNA-m RNA.Interestingly,SOX2,SIX1 and FOXC1 in the subnet are all transcription factors.The subnetwork is regulated by 7 mi RNAs,3 lnc RNAs and 7 circ RNAs in the ceRNA regulatory network.Conclusion: This study firstly reveals the potential mechanism of lnc RNA and circ RNA in the pathogenesis of RIF through a ceRNA regulatory network jointly constructed by lnc RNA and circ RNA.Our study provides further insights into the development of RIF from the perspective of ceRNA mechanisms.