Dataset Information

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis.

ABSTRACT:

Background

This study was aimed at mining crucial long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) for the development of polycystic ovary syndrome (PCOS) based on the coexpression and the competitive endogenous RNA (ceRNA) theories and investigating the underlying therapeutic drugs that may function by reversing the expression of lncRNAs, miRNAs, and mRNAs.

Methods

RNA (GSE106724, GSE114419, GSE137684, and GSE138518) or miRNA (GSE84376 and GSE138572) expression profile datasets of PCOS patients were downloaded from the Gene Expression Omnibus database. The weighted gene coexpression network analysis (WGCNA) using four RNA datasets was conducted to construct the lncRNA-mRNA coexpression networks, while the common differentially expressed miRNAs in two miRNA datasets and module RNAs were used to establish the ceRNA network. A protein-protein interaction (PPI) network was created to explore the potential interactions between genes. Gene Ontology and KEGG pathway enrichment analyses were performed to explore the functions of genes in networks. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) analyses were performed to identify potential therapeutic agents for PCOS.

Results

Three modules (black, magenta, and yellow) were identified to be PCOS-related after WGCNA analysis, in which KLF3-AS1-PLCG2, MAPKAPK5-AS1-MAP3K14, and WWC2-AS2-TXNIP were important coexpression relationship pairs. WWC2-AS2-hsa-miR-382-PLCG2 was a crucial ceRNA loop in the ceRNA network. The PPI network showed that MAP3K14 and TXNIP could interact with hub genes PLK1 (degree = 21) and TLR1 (degree = 18), respectively. These genes were enriched into mitosis (PLK1), immune response (PLCG2 and TLR1), and cell cycle (TXNIP and PLK1) biological processes. Ten small molecule drugs (especially quercetin) were considered to be therapeutical for PCOS.

Conclusion

Our study may provide a novel insight into the mechanisms and therapy for PCOS.

SUBMITTER: Zeng Z

PROVIDER: S-EPMC7666708 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis.

Zeng Zhi Z Lin Xia X Xia Tingting T Liu Wenxiu W Tian Xiaohui X Li Manchao M

BioMed research international 20201106

<h4>Background</h4>This study was aimed at mining crucial long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) for the development of polycystic ovary syndrome (PCOS) based on the coexpression and the competitive endogenous RNA (ceRNA) theories and investigating the underlying therapeutic drugs that may function by reversing the expression of lncRNAs, miRNAs, and mRNAs.<h4>Methods</h4>RNA (GSE106724, GSE114419, GSE137684, and GSE138518) or miRNA (GSE84376 and GSE138572) ...[more]

PMID: 33224973

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Project description:Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, which is characterized by ovulatory dysfunction, clinical and/or biochemical androgen excess, polycystic ovaries on ultrasound and genetic heterogeneity. It was well-accepted that many lncRNAs and mRNAs were associated with PCOS, however, remain unclear. Therefore, the purpose of our study was to examine different expression profiles of lncRNAs and mRNAs in ovarian granulosa cells (GCs) in PCOS and Controls, and identify the correlation between lncRNAs, mRNAs and clinical parameters. Sixty five PCOS patients and 65 Controls were enrolled in this study and adopted standard long agonist protocols or GnRH antagonist protocols. Then 6 GCs samples in each group were subjected to high-thoughput sequencing and the remaining samples were used for the further verification by quantitative real-time PCR (qRT-PCR). Gene Oncology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) enrichment analysis were performed. We predicted the relationship between lncRNAs and mRNAs by Cytoscape software. According to the expression level of lncRNAs, mRNAs and the clinical parameters, we also explored their relationship and evaluate their predictive values for embryos quality and PCOS. We identified 1,049 differential expressed lncRNAs and 3,246 mRNAs (fold-change ≥2, p-value < 0.05). Seven lncRNAs (NONHSAT101926.2, NONHSAT136825.2, NONHSAT227177.1, NONHSAT010538.2, NONHSAT191377.1, NONHSAT230904.1, ENST00000607307) and 3 mRNAs (EREG, ENTPD6, YAP1) were validated consistent with sequence profile. Seven lncRNAs were related to hormone level and follicle counts, 3 mRNAs had connections with lipid metabolism. The area under curve (AUC) of 7 lncRNAs were valuable in distinguishing patients with PCOS from Controls. The AUC of NONHSAT230904.1 and NONHSAT227177.1 were 0.6807 and 0.6410, respectively, for distinguishing whether the rate of high-quality embryos exceeds 50%. Our study showed that the GCs lncRNAs and mRNAs were involved in the occurrence and development of PCOS, which contribute to clarify the pathogenesis mechanism of PCOS.

Project description:BackgroundWomen with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS.Methods and materialsClinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman® Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease.ResultsWomen with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, padj = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, padj = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling.ConclusionsThese studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile.

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Project description:Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women of reproductive age and features complex pathological symptoms and mechanisms. Existing medical treatments have, to some extent, alleviated the deterioration of PCOS. However, these strategies only temporarily control symptoms, with a few side effects and no preventive effect. Phytochemicals extracted from medicinal herbs and plants are vital for discovering novel drugs. In recent years, many kinds of research have proven that phytochemicals isolated from traditional Chinese medicine (TCM) and medicinal plants show significant potential in preventing, alleviating, and treating PCOS. Nevertheless, compared to the abundance of experimental literature and minimal specific-topic reviews related to PCOS, there is a lack of systematic reviews to summarize these advancements in this promising field. Under this background, we systematically document the progress of bioactive phytochemicals from TCM and medicinal plants in treating PCOS, including flavonoids, polyphenols, and alkaloids. According to the literature, these valuable phytochemicals demonstrated therapeutic effects on PCOS supported by in vivo and in vitro experiments, mainly depending on anti-inflammatory, antioxidation, improvement of hormone disorder and insulin resistance (IR), and alleviation of hyperinsulinemia. Based on the current progress, future research directions should emphasize 1) exploring bioactive phytochemicals that potentially mediate bone metabolism for the treatment of PCOS; 2) improving unsatisfactory bioavailability by using advanced drug delivery systems such as nanoparticles and antibody-conjugated drugs, as well as a chemical modification; 3) conducting in-depth research on the pathogenesis of PCOS to potentially impact the gut microbiota and its metabolites in the evolution of PCOS; 4) revealing the pharmacological effects of these bioactive phytochemicals on PCOS at the genetic level; and 5) exploring the hypothetical and unprecedented functions in regulating PCOS by serving as proteolysis-targeting chimeras and molecular glues compared with traditional small molecule drugs. In brief, this review aims to provide detailed mechanisms of these bioactive phytochemicals and hopefully practical and reliable insight into clinical applications concerning PCOS.

Dataset Information

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis.

Background

Methods

Results

Conclusion

Publications

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis.

Similar Datasets

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