Construction of a ceRNA network combining transcription factors in eutopic endometrial tissue of tubal factor infertility and endometriosis-related infertility

Junzui Li, Lulu Ren, Cui Yang, Rongfeng Wu, Zhixiong Huang, Qionghua Chen
2019 · doi:10.21203/rs.2.19312/v1 · W4256360593
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Abstract

Abstract Purpose Although tubal factor infertility (TFI) and endometriosis-related infertility all can result in female infertility, the pathogenesis of TFI and endometriosis-related infertility were different. The pathophysiologic mechanisms of TFI and endometriosis-related infertility have not been investigated thoroughly. Thus, the aim of the study is to identify the potential crucial genes, pathways, transcription factors (TFs) and long non-coding RNAs (lncRNAs) associated with TFI and endometriosis-related infertility, and further analyze the molecular mechanism implicated in genes. Methods 3 patients with TFI and 3 patients with endometriosis-related infertility were recruited, and microarray hybridization of the eutopic endometrial tissue during the window of implantation (WOI) was performed to examine the expression of mRNAs and lncRNAs. First, differentially expressed genes (DEGs) and differentially expressed lncRNAs (DELs) were screened out based on P < 0.05 and fold change (FC) ≧ 2. Second, gene ontology, pathway and TFs enrichment analyses and PPI network construction of DEGs were performed. Then, important modules and Hub genes of PPI network were further analysed and a ceRNA network combining TFs based on DEGs and DELs was constructed. Finally, we selected the lapping genes of the important modules, Hub genes and the ceRNA network as potential key genes associated with TFI and endometriosis-related infertility and constructed a new ceRNA network on the base of potential key genes. Results 508 DEGs and 576 DELs were screened out. The gene ontology and pathway of DEGs were mainly enriched in transmembrane transporter activity and the immune system (eg, passive transmembrane transporter activity, Intestinal immune network for IgA production and so on). In addition, a ceRNA network (based on potential key genes) combining TFs including 2 mRNAs (PLAU and LDLR), 5 miRNAs (hsa-miR-301b-3p, hsa-miR-27a-3p, hsa-miR-20b-5p, hsa-miR-193a-3p and hsa-miR-17-5p), 8 lncRNAs (eg. LMO7-AS1, ITFG3 and MGST1, etc.) and 10 TFs (eg. SRF, FOX, which target to mRNA and eg. POU3F2, HNF1A, which target to miRNA) was successfully built. Conclusions In conclusion, pathophysiologic mechanisms of TFI and endometriosis related infertility may be related to the transmembrane transporter activity and the immune system. These potential key RNAs and TFs might have clinical utility for the diagnosis and prognosis prediction in TFI and endometriosis-related infertility. The results of the current study might lay the foundation for future basic and clinical research.

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endometriosisinfertility

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