Construction of implantation failure related lncRNA-mRNA network and identification of lncRNA biomarkers for predicting endometrial receptivity.
Construction of implantation failure related lncRNA-mRNA network and identification of lncRNA biomarkers for predicting endometrial receptivity.
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着床失败相关lncRNA-mRNA网络的构建及预测子宫内膜容受性的lncRNA生物标志物的鉴定
DOI：
10.7150/ijbs.25081
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发表时间：
2018
影响因子：
9.2
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Feng C;Shen JM;Lv PP;Jin M;Wang LQ;Rao JP;Feng L
子宫内膜容受性不足是导致着床失败的主要因素，传统的子宫内膜形态观察方法不能充分判断子宫内膜容受性的状况。考虑到长非编码RNA(LncRNAs)调节子宫内膜容受性，竞争内源性RNA(CerNA)机制在许多生物学过程中发挥作用，CerNA很可能在IF的病理过程中发挥作用。在本研究中，我们旨在构建一个与植入失败相关的lncRNA-mRNA网络(IFLMN)，并确定关键的lncRNA作为预测子宫内膜容受性的候选基因。根据从lncRNASNP和miRTarBase获得的推测的lncRNA-miRNA和miRNA-mRNA对构建全球背景网络。利用GSE26787的数据计算IF的差异表达基因(Deg)，然后重新注释为差异表达的mRNAs(Dem)和lncRNAs(Dels)。通过超几何实验构建了包含255个lncRNA-mRNA对、10个lncRNAs和212个mRNAs的IFLMN。拓扑分析确定了具有最高质心的关键lncRNA。通过非监督聚类、GO分类、KEGG途径和共表达模块分析，获得了6个关键的lncRNAs及其CENA子网络，它们参与了子宫和准备胚胎植入的子宫内膜的免疫活性、生长因子结合、血管增殖、细胞凋亡和类固醇生物合成。收集黄体中期子宫内膜标本16例，其中复发性着床失败(RIF)或复发性流产(RM)组8例，正常妊娠组8例。用实时荧光定量聚合酶链式反应比较上述6种LncRNAs在RIF/RM患者子宫内膜中的表达，结果表明这些LncRNAs在RIF/RM患者子宫内膜中的表达均显著升高。其潜在机制尚需进一步研究，lncRNAs有可能发展成为预测子宫内膜容受性的生物标志物。
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.
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影响因子：
2.4
作者：
Fan, Li-juan;Han, Hong-jing;Shi, Cheng
通讯作者：
Shi, Cheng
影响因子：
4.8
作者：
Hannan, N. J.;Paiva, P.;Salamonsen, L. A.
通讯作者：
Salamonsen, L. A.
影响因子：
4
作者：
Bourdiec, Amelie;Ahmad, Syed-Furquan;Akoum, Ali
通讯作者：
Akoum, Ali
DOI：
10.1111/aji.12473
发表时间：
2016-03
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Bhurke AS;Bagchi IC;Bagchi MK
通讯作者：
Bagchi MK
影响因子：
5.8
作者：
Gibson, D. A.;McInnes, K. J.;Saunders, P. T. K.
通讯作者：
Saunders, P. T. K.