Construction of implantation failure related lncRNA-mRNA network and identification of lncRNA biomarkers for predicting endometrial receptivity

Abstract

Insufficient endometrial receptivity is a major factor leading to implantation failure (IF), and the traditional way of morphological observation of endometrium cannot determine the condition of receptivity sufficiently. Considering that long-noncoding RNAs (lncRNAs) regulate endometrial receptivity and competing endogenous RNA (ceRNA) mechanism works in plenty of biological processes, ceRNA is likely to function in the pathology of IF. In the present study, we aim to construct an implantation failure related lncRNA-mRNA network (IFLMN), and to identify the key lncRNAs as the candidates for predicting endometrial receptivity. The global background network was constructed based on the presumed lncRNA-miRNA and miRNA-mRNA pairs obtained from lncRNASNP and miRTarBase. Differentially expressed genes (DEGs) of IF were calculated using the data of GSE26787, and then re-annotated as differentially expressed mRNAs (DEMs) and lncRNAs (DELs). IFLMN was constructed by hypergeometric test, including 255 lncRNA-mRNA pairs, 10 lncRNAs, and 212 mRNAs. Topological analysis determined the key lncRNAs with the highest centroid. Functional enrichment analyses were performed by unsupervised clustering, GO classification, KEGG pathway, and co-expression module analyses, achieving six key lncRNAs and their ceRNA sub-networks, which were involved in immunological activity, growth factor binding, vascular proliferation, apoptosis, and steroid biosynthesis in uterus and prepared endometrium for embryo implantation. Sixteen endometrial samples were collected during mid-luteal phase, including 8 recurrent implantation failure (RIF) or recurrent miscarriage (RM) women and 8 controls who conceived successfully. Quantitative real-time PCR was performed to compare the expression of the above six lncRNAs, which validated that the expression of all these lncRNAs was significantly elevated in endometrium of RIF/RM patients. Further studies are needed to investigate the underlying mechanism, and the lncRNAs may be developed into predictive biomarkers for endometrial receptivity.

Identification of Key lncRNAs Associated With Atherosclerosis Progression Based on Public Datasets

“…In previous studies, many groups conducted bioinformatics analysis for lncRNAs using their co-expressing genes. For instance, Feng et al (2018) identified and predicted the functions of implantation failure related lncRNAs by constructing the lncRNA-mRNA co-expression network. In order to study the potential functions of atherosclerosis-related lncRNAs, we performed WGCNA analysis.…”

Association between the rs2288947 polymorphism of the lncRNA TINCR gene and the risk of recurrent miscarriage in a Southern Chinese population

“…Although the specific functions of most lncRNAs are still unknown, recent studies have shown that lncRNAs play an important role in the development and progression of abortion . Feng et al clarified that many lncRNAs are abnormally expressed in patients with recurrent spontaneous abortion and that lncRNA can be used as a biomarker for predicting recurrent spontaneous abortion. A study by Zhang et al suggested that lncRNAs HOTAIR may be a potential therapeutic target for recurrent miscarriage.…”

“…,23 Feng et al24 clarified that many lncRNAs are abnormally expressed in patients with recurrent spontaneous abortion and that lncRNA can be used as a biomarker for predicting recurrent spontaneous abortion. A studyby Zhang et al 25 suggested that lncRNAs HOTAIR may be a potential therapeutic target for recurrent miscarriage.…”

A Novel Molecule in Human Cyclic Endometrium: LncRNA TUNAR Is Involved in Embryo Implantation

“…Long noncoding RNAs (lncRNAs) are more than 200 nucleotides in length and do not code for proteins (Ponting et al, 2009), and involved in the regulation of diverse biological processes including carcinogenesis, epigenetic regulation, and embryonic development (Wapinski and Chang, 2011;Batista and Chang, 2013). Using high-throughput sequencing analysis, recent studies have attempted to uncover key lncRNAs as biomarkers to predict endometrial receptivity (Koot et al, 2016;Fan et al, 2017;Sigurgeirsson et al, 2017;Chen et al, 2018Chen et al, , 2019Feng et al, 2018), while little is known about their biological function and significance in the human endometrium. The expression of H19 was down-regulated in the endometrium of RIF (Zeng et al, 2017).…”