Research Paper Volume 13, Issue 6 pp 8481—8496
Construction of a ceRNA-based lncRNA-mRNA network to identify functional lncRNAs in polycystic ovarian syndrome
- 1 Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- 2 Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- 3 Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Received: October 6, 2020 Accepted: December 23, 2020 Published: March 10, 2021https://doi.org/10.18632/aging.202659
How to Cite
Copyright: © 2021 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of childbearing age. Recent studies suggest important roles for lncRNAs in PCOS development. Based on the hypothesis that lncRNAs are able to regulate mRNA functions by competitive binding to shared miRNAs, the present work sought to construct a PCOS-related lncRNA-mRNA network (PCLMN) to identify key lncRNAs with dysregulated expression and potential prognostic and therapeutic relevance. A global background network was constructed after retrieving lncRNA-miRNA and miRNA-mRNA pairs from the lncRNASNP2, miRTarBase and StarBase databases. Based on gene expression profiles from ovarian granulosa cells from PCOS patients and controls in the GEO’s GSE95728 dataset, the PCLMN was then constructed by applying hypergeometric testing. Using topological analysis, we identified 3 lncRNAs (LINC00667, AC073172.1 and H19) ranking within the top-ten gene lists for all three centrality measures. We then explored their subcellular localization, performed functional module analyses, and identified 4 sex hormone-related transcription factors as potential regulators of their expression. Significant associations with inflammation, oxidative stress, and apoptosis-related processes and pathways were revealed for the key lncRNAs in our PCMLN. Further studies verifying the mRNA/lncRNA relationships identified herein are needed to clarify their clinical significance.
ceRNA: Competitive endogenous ribonucleic acid; DAVID: Database for Visualization, Annotation and Integrated Discovery; DEGs: differentially expressed genes; DELs: differentially expressed lncRNAs; DEMs: differentially expressed mRNAs; GEO: Gene Expression Omnibus; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; IR: insulin resistance; IRS-1: insulin substrate 1; lncRNA: Long non-coding ribonucleic acid; MCODE: Molecular Complex Detection; mRNA: messenger ribonucleic acid; miRNA: micro-ribonucleic acid; PCLMN: PCOS-related lncRNA-mRNA network; PCOS: Polycystic ovary syndrome; RMA: Robust Multi-Array Average.