The lncRNA-miRNA-mRNA ceRNA network in mural granulosa cells of patients with polycystic ovary syndrome: an analysis of Gene Expression Omnibus data

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine abnormalities in women of reproductive age. In this study, we set out to construct a molecular long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network according to the competitive endogenous RNA (ceRNA) theory and obtain insights into the related biological characteristics and pathways. Methods: We downloaded two gene expression profile datasets of mural granulosa cells (MGCs) of women with PCOS and healthy women without PCOS (GSE84376 and GSE106724) from Gene Expression Omnibus (GEO) DataSets. Using GEO2R, we identified the mRNAs and non-coding RNAs with differential expression. The DIANA-microT-CDS algorithm was applied to predict the genes targeted by the differentially expressed miRNAs. The lncRNA-miRNA interactions were predicted using DIANALncBase v2. Then, we constructed the lncRNA-miRNA-mRNA network. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed to identify the functions and enriched pathways of the genes. Subsequently, STRING was used to construct the protein-protein interaction (PPI) network. cytoHubba in Cytoscape was used to rank the hub genes, and finally, PPI modules were screened with Cytoscape MCODE. Results: There were 462 mRNAs, 2,464 lncRNAs, and 55 miRNAs which showed differential expression between the MGCs of patients with PCOS and those of healthy controls. Based on the PPI analysis, differentially expressed genes (DEGs) were significantly enriched in retinol metabolism, drug metabolism- cytochrome P450, malaria, the Hippo signaling pathway, and glycine, serine, and threonine metabolism. The ceRNA network contained 71 lncRNA nodes, 14 miRNA nodes, and 69 mRNA nodes, as well as 167 edges. We identified some novel genes and non-coding RNAs that might be involved in PCOS, including CD163, MRC1, VSIG4, CCL2, CCR2, SPP1, hsa-miR-3135b, hsa-miR-4649-3p, hsa-miR-1231, hsa-miR-3609, and hsamiR-4433b-3p. Conclusions: This study identified a novel lncRNA-miRNA-mRNA network based on the ceRNA mechanism in PCOS. Some novel genes and non-coding RNAs that may be involved in the occurrence and development of PCOS were excavated, including CD163, MRC1, VSIG4, CCL2, CCR2, SPP1, hsa-miR3135b, hsa-miR-4649-3p, hsa-miR-1231, hsa-miR-3609, and hsa-miR-4433b-3p. However, our findings need to be validated by in vivo and in vitro experiments.

Automated summary

This study constructed a novel lncRNA-miRNA-mRNA network in PCOS based on the ceRNA mechanism, identifying some new genes and non-coding RNAs that may be involved in the occurrence and development of PCOS. However, the findings need validation through in vivo and in vitro experiments.