Construction of a ceRNA network in polycystic ovary syndrome (PCOS) driven by exosomal lncRNA

Abstract

Polycystic ovary syndrome (PCOS), a common and frustrating syndrome in women of reproductive age, is characterized by symptoms including hyperandrogenemia, ovulation dysfunction, and polycystic ovaries. The role of competitive endogenous RNA (ceRNA) networks is receiving increasing attention and has been reported in multiple complicated diseases, such as various carcinomas, endometriosis, and tubal factor infertility. However, the association of ceRNA networks with the pathogenesis of PCOS remains unclear. This study aimed to construct a ceRNA network orchestrated by exosomal lnRNA and circRNA in PCOS. We screened RNA data of 34 samples from the Gene Expression Omnibus (GEO) database for differentially expressed lncRNAs (DELs), miRNAs (DEMs), mRNAs (DEGs), and circRNA associated with the progression of PCOS (PCOS, n = 17 vs. normal, n = 17). A protein–protein interaction (PPI) network, gene set enrichment analysis (GSEA), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Importantly, the function of the ceRNA network was explored using GO and KEGG enrichment analyses. We identified 46 DELs (25 upregulated and 21 downregulated), 31 DEMs (20 upregulated and 11 downregulated), 165 DEGs (52 upregulated and 113 downregulated), and 1 differentially expressed circRNA. The PPI network had 79 nodes and 112 edges. The GSEA results showed that these genes were mainly related to oxidative phosphorylation; TNF signaling pathways; and valine, leucine, and isoleucine degradation. GO and KEGG analyses revealed that the DEGs were significantly enriched in lipid metabolism, peroxisome proliferator-activated receptor (PPAR) signaling pathways, and fatty acid metabolism. Additionally, we constructed a novel PCOS-associated lncRNA–miRNA–mRNA ceRNA triple network and a circRNA-related network. Thereafter, we described the potential roles played by follicular fluid exosomes in PCOS. Our present study describes the molecular pathogenesis of PCOS in human ovarian granulosa cells at the post-transcriptional level, which provides new insights for the clinical diagnosis and treatment of PCOS and further scientific research.

Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome

“…To date, there have only been a few investigations on follicular fluid exosomes in PCOS patients. According to Lilian Bai et al [ 4 ], fatty acid metabolism, peroxisome proliferator-activated receptor (PPAR) signaling pathways, and lipid metabolism were significantly enriched in the various expression genes of follicular fluid exosomes between PCOS and control. The follicular fluid exosomal miRNAs hsa-miR-196a-3p, hsa-miR-143-5p, hsa-miR-106a-3p, hsa-miR-34a-5p, and hsa-miR-20a-5p were possible biomarkers for the diagnosis of PCOS, as revealed by Ye Tian-Min et al [ 21 ].…”

“…Exosomes are tiny, membrane-enclosed vesicles with diameters between 30 and 200 nm released by various live cells in both physiologically healthy and pathological conditions. Recently, a growing number of studies have demonstrated that exosomes are present in FF and function as message transmitters in intercellular communication by transmitting a range of proteins, lipids, miRNAs, and circRNAs [ 4 – 6 ].…”

Silencing LncRNA SNHG16 suppresses the diabetic inflammatory response by targeting the miR-212-3p/NF-κB signaling pathway

“…We also explored the mechanism of SNHG16 in diabetes. The main mechanism of LncRNAs is through the competitive binding mechanism of miRNAs [ 27 , 28 ], and LncRNA H19/miR-675 and LncRNA NEAT1/miR-204 have been reported to interact in a competitive binding manner in breast cancer [ 29 ]. Therefore, we searched for the downstream miRNA of SNHG16.…”

Intercellular communication in the cumulus–oocyte complex during folliculogenesis: A review

“…EVs can transport numerous ribosome and RNA-binding proteins. Recently, more studies focused on other molecules like lipids and lncRNAs ( da Silveira et al, 2021 ; Bai et al, 2022 ). Obviously, EVs play an important role in the folliculogenesis.…”

“…By studying changes in cell interactions, we could tell which synthesized substances are impaired in oocytes and CCs because of aging. A recent study constructed a ceRNA network with regard to exosomes in follicular fluid and revealed a variety of lncRNAs related to the pathogenesis of PCOS ( Bai et al, 2022 ). In general, many respects of the PCOS pathogenesis, like lipid metabolism and chronic inflammation, were included and united into one integrity.…”