Dataset Information

Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis.

ABSTRACT:

Objective

Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS.

Methods

PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro.

Results

NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis.

Conclusion

Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.

SUBMITTER: Zhen J

PROVIDER: S-EPMC8281489 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPolycystic 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.MethodsWe 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 DIANA-LncBase 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.ResultsThere 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 hsa-miR-4433b-3p.ConclusionsThis 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-miR-3135b, 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.