Long non-coding RNAs: novel players in the pathogenesis of polycystic ovary syndrome

Tu, Mixue; Wu, Yiqing; Mu, Liangshan; Zhang, Dan

doi:10.21037/atm-20-5044

Cited by 20 publications

(9 citation statements)

References 77 publications

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“…Furthermore, epigenetic modifications in the pathogenesis of PCOS have come into the focus of interest, and changes in DNA methylation have been observed in the serum, ovaries, hypothalamus, skeletal muscle and adipose tissue of PCOS patients [ 101 , 102 ]. Transcriptomics allow the identification of aberrantly expressed genes in the granulosa or cumulus cells of women with PCOS and have already revealed genes with altered expressions, including non-coding RNAs, such as miRNAs and lncRNAs, which might contribute to ovarian dysfunction [ 103 , 104 ]. Finally, proteomics are used, e.g., to identify novel protein biomarkers in the serum or follicular fluid (FF) of PCOS patients.…”

Section: Polycystic Ovary Syndromementioning

confidence: 99%

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

Schüler-Toprak¹,

Ortmann²,

Buechler³

et al. 2022

Biomedicines

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Polycystic ovary syndrome (PCOS) and endometriosis are frequent diseases of the female reproductive tract causing high morbidity as they can significantly affect fertility and quality of life. Adipokines are pleiotropic signaling molecules secreted by white or brown adipose tissues with a central role in energy metabolism. More recently, their involvement in PCOS and endometriosis has been demonstrated. In this review article, we provide an update on the role of adipokines in both diseases and summarize previous findings. We also address the results of multi-omics approaches in adipokine research to examine the role of single nucleotide polymorphisms (SNPs) in genes coding for adipokines and their receptors, the secretome of adipocytes and to identify epigenetic alterations of adipokine genes that might be conferred from mother to child. Finally, we address novel data on the role of brown adipose tissue (BAT), which seems to have notable effects on PCOS. For this review, original research articles on adipokine actions in PCOS and endometriosis are considered, which are listed in the PubMed database.

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Section: Polycystic Ovary Syndromementioning

confidence: 99%

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

Schüler-Toprak¹,

Ortmann²,

Buechler³

et al. 2022

Biomedicines

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“…FF is filled with a variety of vesicles and molecules, including exosomes, which largely contribute to follicular development and ovum maturation [ 8 ]. Studies have proven that some nucleic acids and proteins in FF are closely involved in follicular glucose metabolism, lipoprotein metabolism, cell proliferation and other processes in patients with PCOS [ 9 – 11 ]. FF-derived exosomes are the main carriers of these nucleic acids and proteins.…”

Section: Introductionmentioning

confidence: 99%

Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome

et al. 2022

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Objective Polycystic ovary syndrome (PCOS) is characterized by follicular dysplasia. An insufficient glycolysis-derived energy supply of granulosa cells (GCs) is an important cause of follicular dysplasia in PCOS. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been proven to regulate the function of GCs. In this study, exosomes extracted from clinical FF samples were used for transcriptome sequencing (RNA-seq) analysis, and a human ovarian granulocyte tumour cell line (KGN cells) was used for in vitro mechanistic studies. Methods and results In FF exosomal RNA-seq analysis, a decrease in glycolysis-related pathways was identified as an important feature of the PCOS group, and the differentially expressed miR-143-3p and miR-155-5p may be regulatory factors of glycolysis. By determining the effects of miR-143-3p and miR-155-5p on hexokinase (HK) 2, pyruvate kinase muscle isozyme M2 (PKM2), lactate dehydrogenase A (LDHA), pyruvate, lactate and apoptosis in KGN cells, we found that upregulated miR-143-3p expression in exosomes from the PCOS group inhibited glycolysis in KGN cells; knockdown of miR-143-3p significantly alleviated the decrease in glycolysis in KGN cells in PCOS. MiR-155-5p silencing attenuated glycolytic activation in KGN cells; overexpression of miR-155-5p significantly promoted glycolysis in KGN cells in PCOS. In this study, HK2 was found to be the mediator of miR-143-3p and miR-155-5p in FF-derived exosome-mediated regulation of glycolysis in KGN cells. Reduced glycolysis accelerated apoptosis of KGN cells, which mediated follicular dysplasia through ATP, lactate and apoptotic pathways. Conclusions In conclusion, these results indicate that miR-143-3p and miR-155-5p in FF-derived exosomes antagonistically regulate glycolytic-mediated follicular dysplasia of GCs in PCOS.

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“…LncRNAs are a class of transcripts (>200 nucleotides) lacking protein-coding capacity, and they function as competitive endogenous RNAs (ceRNAs) and are significantly correlated with some clinical phenotypes in PCOS [ 30 ]. Previous studies have found that the expression levels of RDH10-AS1, NARF-IT1, AC090617.1, MZF1-AS1, AC009495.2, LINC01564, AQP4-AS1, L34079.3, OSBPL10-AS1, PIK3CD-AS2, LINC01181, and LINC00907 were reduced in PCOS [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Transcriptomic and Metabolomic Analysis of Women with Polycystic Ovary Syndrome

Lin

Ding

et al. 2022

Disease Markers

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Background. Polycystic ovary syndrome (PCOS) is a complex class of endocrine disorders with insulin resistance, compensatory hyperinsulinemia, and obesity. However, the pathogenesis and therapies of PCOS have not been fully elucidated. Exosomal miRNAs have the potential to serve as biomarkers and therapies for a wide range of medical conditions. Method. We collected follicular fluid from 5 PCOS patients and 5 healthy people. High-throughput sequencing technology to identify differentially expressed miRNAs and untargeted metabolome identify differential metabolites in follicular fluid exosomal. RT-qPCR and AUC analysis were performed. Result. miRNA high-throughput sequencing identified 124 differential miRNAs. RT-qPCR analysis confirmed the sequencing results. These differential miRNA target genes are mainly involved in metabolic pathways. Metabolomics studies identified 31 differential metabolites. miRNA and lncRNA coexpression networks in metabolic pathways rigorously screened 28 differentially expressed miRNAs. This network would identify miRNA signatures associated with metabolic processes in PCOS. Meanwhile, the area under curve of receiver operating characteristic revealed that hsa-miR-196a-3p, hsa-miR-143-5p, hsa-miR-106a-3p, hsa-miR-34a-5p, and hsa-miR-20a-5p were potential biomarkers for the diagnosis of PCOS. Conclusion. Collectively, these results demonstrate the potential pathogenesis of PCOS, and follicular fluid exosomal miRNAs may be efficient targets for the diagnosis and treatment of PCOS in long-term clinical studies.

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Long non-coding RNAs: novel players in the pathogenesis of polycystic ovary syndrome

Cited by 20 publications

References 77 publications

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome

Combined Transcriptomic and Metabolomic Analysis of Women with Polycystic Ovary Syndrome

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