Construction of lncRNA-related competing endogenous RNA network and identification of hub genes in recurrent implantation failure

Reproductive Biology and Endocrinology

Ning Song¹  Leizhen Xia²  Lifeng Tian²  Qiongfang Wu²  Jun Tan²  Jialyu Huang²  Qianqian Chen³  Jing Zhu³ 

[1] Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China;Reproductive Medical Center, Jiangxi Provincial Maternal and Child Health Hospital, 330006, Nanchang, China;Reproductive Medical Center, The First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, China;

关键词: Recurrent implantation failure;    Long non-coding RNA;    Competing endogenous RNA;    Weighted gene co-expression network analysis;   

DOI  :  10.1186/s12958-021-00778-1

来源: Springer

【 摘 要 】

BackgroundThe mechanism of recurrent implantation failure (RIF) is unclear at present and poor endometrial receptivity may be one of the leading reasons. This study aims to construct a competing endogenous RNA (ceRNA) network and identify potential hub genes underlying the development of RIF.MethodsWeighted gene co-expression network analysis was performed based on differentially expressed mRNAs (DEMs) and lncRNAs (DELs) from the GSE111974 dataset. Functional enrichment analyses of gene modules were conducted using Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway. A lncRNA-miRNA-mRNA ceRNA regulatory network was constructed according to predictive interaction derived from the LncRNADisease, miRTarBase, miRDB and TargetScan databases. Topological analysis determined the key genes with the highest centroid and their expressions were further verified using public datasets and quantitative real-time polymerase chain reaction.ResultsA total of 1500 DEMs and 3 DELs were significantly up-regulated, whereas 1022 DEMs and 4 DELs were significantly down-regulated in the RIF group compared with the control group. Six functional co-expression modules were enriched in various biological processes, such as cell adhesion, regulation of cell motility and cellular response to vascular endothelial growth factor stimulus. Five hub genes were identified in the ceRNA network, of which GJA1 was down-regulated whereas TET2, MAP2K6, LRRC1 and TRPM6 were up-regulated in RIF endometrium.ConclusionsWe constructed a lncRNA-associated ceRNA network and identified five novel hub genes in RIF. This finding could be helpful to understand the molecular mechanism for RIF pathogenesis, and may provide novel insights for its early diagnosis and treatment.

【 授权许可】

CC BY