Exosomal lncRNA-miRNA-mRNA regulatory axis may drive inflammation in polycystic ovary syndrome.
TL;DR
A potential role for dysregulation of the exosomal lncRNA-miRNA-mRNA regulatory axis, particularly involving IL-6 and TGF-β1 mRNA expression, in the inflammatory processes associated with PCOS is suggested.
Abstract
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in reproductive-aged women and is associated with reproductive dysfunction, metabolic abnormalities, and chronic low-grade inflammation. Emerging evidence highlights the role of circulating exosomal inflammatory cytokines and non-coding RNAs (ncRNAs) in PCOS pathogenesis. This case-control study aimed to investigate the expression of exosomal mRNA expression levels of IL-6 and TGF-β1, and selected long non-coding RNAs (MALAT1, NEAT1, H19, GAS5, and HOTAIR) in women with PCOS and to elucidate the associated lncRNA-miRNA-mRNA regulatory network. Exosomes were isolated from serum samples of PCOS and healthy subjects using a commercial exosome isolation kit. Exosomes were characterized by FESEM, DLS, zeta potential analysis, and flow cytometry, followed by RNA extraction and cDNA synthesis. Bioinformatic analyses were performed to construct regulatory networks, followed by molecular docking to evaluate the potential interactions between lncRNAs and miRNAs. A heatmap illustrating gene expression patterns was generated in R using the pheatmap package. Characterization of the isolated vesicles confirmed a spherical morphology, nanoscale dimensions, and the presence of exosomal surface markers. The exosomal mRNA expression levels of IL-6 and TGF-β1 were significantly upregulated in patients with PCOS. Among the lncRNAs analyzed, GAS5, NEAT1, and H19 were significantly increased, whereas MALAT1 and HOTAIR were markedly decreased. Network analysis identified miR-146a-5p and miR-29b-3p as key regulatory hubs associated with IL-6 and TGF-β1 mRNA expression. Molecular docking suggested a higher likelihood of stable binding, particularly for the H19/miR-146a-5p and NEAT1/miR-29b-3p complexes. These findings may suggest a potential role for dysregulation of the exosomal lncRNA-miRNA-mRNA regulatory axis, particularly involving IL-6 and TGF-β1 mRNA expression, in the inflammatory processes associated with PCOS. In addition, circulating exosomal ncRNAs and inflammation-related factors may represent potential non-invasive biomarkers and possible therapeutic targets for PCOS. However, these associations require further functional and validation studies.