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. 2021 Jun 9:2021:9988347.
doi: 10.1155/2021/9988347. eCollection 2021.

Bioinformatics Analysis of ceRNA Network Related to Polycystic Ovarian Syndrome

Yuanqi Li  1 , Yong Tan  2
Affiliations

Bioinformatics Analysis of ceRNA Network Related to Polycystic Ovarian Syndrome

Yuanqi Li et al. Comput Math Methods Med. .

Abstract

Introduction: Polycystic ovary syndrome (PCOS) is caused by the hormonal environment in utero, abnormal metabolism, and genetics, and it is common in women of childbearing age. A large number of studies have reported that lncRNA is important to the biological process of cancer and can be used as a potential prognostic biomarker. Thus, we studied lncRNAs' roles in PCOS in this article.

Methods: We obtained mRNAs', miRNAs', and lncRNAs' expression profiles in PCOS specimens and normal specimens from the National Biotechnology Information Gene Expression Comprehensive Center database. The EdgeR software package is used to distinguish the differentially expressed lncRNAs, miRNAs, and mRNAs. Functional enrichment analysis was carried out by the clusterProfiler R Package, and the lncRNA-miRNA-mRNA interaction ceRNA network was built in Cytoscape plug-in BiNGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively.

Results: We distinguished differentially expressed RNAs, including 1087 lncRNAs, 14 miRNAs, and 566 mRNAs in PCOS. Among them, 410 lncRNAs, 11 miRNAs, and 185 mRNAs were contained in the ceRNA regulatory network. The outcomes from Gene Ontology (GO) analysis showed that the differentially expressed mRNAs (DEMs) were mainly enriched in response to the maternal process involved in female pregnancy, morphogenesis of embryonic epithelium, and the intracellular steroid hormone receptor signaling pathway. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis data showed that DEMs were primarily enriched in pathways related to the TGF-β signaling pathway, Type I diabetes mellitus, and glycolysis/gluconeogenesis. In addition, we chose NONHSAT123397, ENST00000564619, and NONHSAT077997 as key lncRNAs due to their high bearing on PCOS.

Conclusion: ceRNA networks play an important role in PCOS. The research indicated that specific lncRNAs were related to PCOS development. NONHSAT123397, ENST00000564619, and NONHSAT077997 could be regarded as potential diagnostic mechanisms and biomarkers for PCOS. This discovery might provide more effective and more novel insights into the mechanisms of PCOS worthy of further exploration.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The reconstruction of the lncRNA-miRNA-mRNA network. Firstly, expression data of miRNA, lncRNA, and mRNA were downloaded from the Gene Expression Omnibus. Secondly, DEMs (differentially expressed mRNAs), DELs (differentially expressed lncRNAs), and DEMis (differentially expressed miRNAs) were screened at ∣fold change)∣>2 and false discovery rate (FDR) < 0.05. Thirdly, target lncRNAs of DEMis were predicted using RNAhybrid and miRanda, and target mRNAs of DEMis were predicted using miRTarBase and miRWalk. Fourthly, the coexpression lncRNAs and coexpression mRNAs were obtained to merge the target lncRNAs and mRNAs of DEMis with DELs and DEMs, respectively. Finally, the coexpression lncRNAs, DEMis, and coexpression mRNAs were mapped into the interactions.
Figure 2
Figure 2
The lncRNA-miRNA interaction network. There were 410 lncRNAs, 11 miRNAs, and 691 edges in the network. The square stands for lncRNA and the circle stands for miRNA. All shapes in red stand for upregulation, and green stand for downregulation.
Figure 3
Figure 3
The miRNA-mRNA interaction network. There were 10 miRNAs, 185 mRNAs, and 449 edges in the network. The rhombus stands for mRNA, and the circle stands for miRNA. All shapes in red stand for upregulation, and those in green stand for downregulation.
Figure 4
Figure 4
The dysregulated lncRNA-mRNA-miRNA ceRNA network. There were 410 lncRNAs, 10 miRNAs, 185 mRNAs, and 1079 edges in the network. The square stands for lncRNA, the rhombus stands for mRNA, and the circle stands for miRNA. All shapes in red stand for upregulation, and those in green stand for downregulation.
Figure 5
Figure 5
The enriched GO terms of the genes involved in the ceRNA network in PCOS. The x-axis stands for the enrichment factor of the indicated genes, and the y-axis stands for the top 30 GO terms. The circle denotes the biological process term, the triangle denotes the cellular component term, and the square denotes the molecular function term. The gradient of green to red denotes a change in the significance of the correlation from low to high. The different sizes of the dots denote related mRNA numbers.
Figure 6
Figure 6
The enriched KEGG pathways of the genes involved in the ceRNA network in PCOS. The x-axis stands for the enrichment factor of the indicated genes, and the y-axis stands for the top 30 KEGG pathways. The circle denotes the biological process term, the triangle denotes the cellular component term, and the square denotes the molecular function term. The gradient of green to red denotes a change in the significance of the correlation from low to high. The different sizes of the dots denote related mRNA numbers.
Figure 7
Figure 7
All node degree analysis reveals specific properties of the lncRNA-miRNA-mRNA network.
Figure 8
Figure 8
The subnetwork of lncRNA NONHSAT123397. The square stands for lncRNA, the rhombus stands for mRNA, and the circle stands for miRNA. All shapes in red stand for upregulation, and those in green stand for downregulation.
Figure 9
Figure 9
The subnetwork of lncRNA ENST00000564619. The square stands for lncRNA, the rhombus stands for mRNA, and the circle stands for miRNA. All shapes in red stand for upregulation, and those in green stand for downregulation.
Figure 10
Figure 10
The subnetwork of lncRNA NONHSAT077997. The square stands for lncRNA, the rhombus stands for mRNA, and the circle stands for miRNA. All shapes in red stand for upregulation, and those in green stand for downregulation.
Figure 11
Figure 11
The top 30 significantly enriched GO terms (a) and KEGG pathways (b) of lncRNA NONHSAT123397-miRNA-mRNA subnetwork-related mRNAs.
Figure 12
Figure 12
The top 30 significantly enriched GO terms (a) and KEGG pathways (b) of lncRNA ENST00000564619-miRNA-mRNA subnetwork-related mRNAs.
Figure 13
Figure 13
The top 30 significantly enriched GO terms (a) and KEGG pathways (b) of lncRNA NONHSAT077997-miRNA-mRNA subnetwork-related mRNAs.
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