Novel Hub genes co-expression network mediates dysfunction in a model of polycystic ovary syndrome

Am J Transl Res. 2022 Mar 15;14(3):1979-1990. eCollection 2022.

Abstract

Background: This study aimed to integrate DNA methylation, miRNA, and mRNA microarray data to construct a gene co-expression network for polycystic ovarian syndrome (PCOS).

Methods: The weighted gene co-expression network analysis (WGCNA) was conducted to construct a PCOS-related co-expression network by using the GEO public datasets. We performed Gene Ontology and KEGG pathway enrichment analyses for a further exploration of gene function in networks. Finally, the dysfunction module consisting of a co-expression network was mapped to the PCOS patients and tried to provide guidance to the PCOS phenotyping.

Results: Three modules (Midnightbule, Pink, and Red) were identified to be PCOS-related by WGCNA analysis. These module-related genes were enriched in cell response to stimulus, PI3K-Akt signaling pathway, insulin biological process, signaling pathway, and cytokine-cytokine receptor interaction biological processes. The multiple-factor network, including miRNA-lncRNA and DNA methylation-mRNA interaction, was closely associated with PCOS dysfunction.

Conclusion: Our study render a novel insight into the mechanisms and might provide candidate biomarkers and therapeutic targets for the classification of PCOS dysfunction.

Keywords: DNA methylation-mRNA network; Polycystic ovarian syndrome; dysfunction phenotype; miRNA-lncRNA; reproductive disorder.