Role of microRNA in the Pathogenesis of Polycystic Ovary Syndrome

Chen, Zhuo; Ou, Han-Xiao; Wu, Hongliang; Wu, Peng; Zhang, Mo

doi:10.1089/dna.2019.4622

Cited by 35 publications

(25 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, we found that miR-3585-5p and miR-30-5p were significantly upregulated, and miR-146-5p was downregulated in the LEHF group, which was consistent with the deep sequencing results. MiR-30 was significantly upregulated in ovaries from PCOS with insulin resistance rats which is consistent with previous studies [28,41,42]. However, miR-146 was significantly upregulated in serum from PCOS patients compared with that of healthy women, which is inconsistent with our findings [28,42].…”

Section: Discussioncontrasting

confidence: 54%

MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance

Zhang

Lin

et al. 2020

Arch Gynecol Obstet

View full text Add to dashboard Cite

Purpose The present study established microRNA (miRNA) expression profiles for rat ovaries displaying polycystic ovary syndrome (PCOS) with insulin resistance and explored the underlying biological functions of differentially expressed miRNAs. Methods A PCOS with insulin resistance rat model was created by administering letrozole and a high-fat diet. Total RNA was extracted from the ovaries of PCOS with insulin resistance rats and normal rats. Three ovaries from each group were used to identify differentially expressed miRNAs by deep sequencing. A hierarchical clustering heatmap and volcano plot were used to display the pattern of differentially expressed miRNAs. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the potential target genes of the differentially expressed miRNAs and identify their putative biological function. Nine of the differentially expressed miRNAs were selected for validation by Real-time Quantitative PCR (qRT-PCR). Results A total of 58 differentially expressed miRNAs were identified in the rat ovaries exhibiting PCOS with insulin resistance compared with control ovaries, including 23 miRNAs that were upregulated and 35 miRNAs that were downregulated. GO and KEGG pathway analyses revealed that the predicted target genes were related to metabolic processes, cellular processes, and metabolic pathways. Furthermore, qRT-PCR confirmed that miR-3585-5p and miR-30-5p were significantly upregulated and miR-146-5p was downregulated in the ovaries of PCOS with insulin resistance rats compared with the controls. Conclusion These results indicate that differentially expressed miRNAs in rat ovaries may be involved in the pathophysiology of insulin resistance in PCOS. Our study may be beneficial in establishing miRNAs as novel diagnostic and therapeutic biomarkers for insulin resistance in PCOS.

show abstract

Section: Discussioncontrasting

confidence: 54%

MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance

Zhang

Lin

et al. 2020

Arch Gynecol Obstet

View full text Add to dashboard Cite

show abstract

“…69,70 Chen et al have extensively discussed the role of miRNA in PCOS. 71 Muri et al have previously shown that levels of miR-21, miR-103 and miR-155 were positively associated with levels of free testosterone in women with PCOS 72 and several miRNAs have been shown to be negatively correlated with levels of testosterone and A4 in these women. 73,74 Moreover, comparing miR-130b-3p in normal and theca cells of women with PCOS have shown a decreased expression in PCOS which was correlated with increased expression of CYP17A1 and DHEA synthesis, which may contribute to the androgen excess in PCOS.…”

Section: Peripheral Tissues and Androgen Excessmentioning

confidence: 96%

“…188,189 These expressions have been investigated in women with PCOS in the context of insulin resistance (IR). 71 miR-222 has been shown to be positively associated with hyperinsulinaemia in women with PCOS, suggesting its role in IR in PCOS. 69 Treating an IR adipose tissue cell line with high levels of glucose and insulin increased levels of miR-320 significantly which in turns reversed the IR via increasing the expression of GLUT4.…”

Section: Androgens In Metabolic Target Tissuesmentioning

confidence: 99%

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome

Kempegowda

Melson

Manolopoulos

et al. 2020

Therapeutic Advances in Endocrinology

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) has been traditionally perceived as a reproductive disorder due to its most common presentation with menstrual dysfunction and infertility. However, it is now clear that women with PCOS are at increased risk of metabolic dysfunction, from impaired glucose tolerance and type 2 diabetes mellitus to nonalcoholic fatty liver disease and cardiovascular disease. PCOS is characterised by androgen excess, with cross-sectional data showing that hyperandrogenism is directly complicit in the development of metabolic complications. Recent studies have also shown that C11-oxy C19 androgens are emerging to be clinically and biochemically significant in PCOS, thus emphasising the importance of understanding the impact of both classic and C11-oxy C19 androgens on women’s health. Here we discuss androgen metabolism in the context of PCOS, and dissect the role played by androgens in the development of metabolic disease through their effects on metabolic target tissues in women.

show abstract

“…Recently, the role of miRNAs in the pathogenesis of PCOS has attracted increasing attention (22). Altered miRNA expression profiles in patients with PCOS have been regarded as biomarkers and therapeutic targets for PCOS (22,23). Testosterone-induced GC apoptosis is involved in the pathological development of PCOS (7).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑874‑3p promotes testosterone‑induced granulosa cell apoptosis by suppressing HDAC1‑mediated p53 deacetylation

Wei

Wang

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

MicroRNA (miR)-874-3p is a newly identified miRNA that is involved in several pathological processes, including cancer, myocardial infarction, bone formation and erectile dysfunction. However, the role of miR-874-3p in polycystic ovary syndrome (PCOS) and granulosa cell (GC) apoptosis is not completely understood. The present study investigated the expression profile of miR-874-3p in PCOS by reverse transcription- quantitative PCR and the GC apoptosis by flow cytometry analysis. miR-874-3p expression was significantly upregulated in GCs isolated from patients with PCOS compared with patients without PCOS. In addition, miR-874-3p expression was positively correlated with GC apoptosis and testosterone levels in both patients with PCOS and patients without PCOS. Therefore, the present study also aimed to investigate the effects of miR-874-3p on testosterone-induced GC apoptosis. Compared with vehicle-treated GCs, miR-874-3p expression levels were significantly increased in testosterone-treated GCs, which was inhibited by the androgen receptor antagonist flutamide. GCs were transfected with either the miR-874-3p mimic or a miR-874-3p inhibitor. Compared with the control group, miR-874-3p mimic significantly enhanced GC apoptosis, whereas miR-874-3p inhibitor significantly decreased GC apoptosis. Moreover, histone deacetylase (HDAC) activity and HDAC1 expression levels were decreased in testosterone-treated GCs compared with vehicle-treated GCs. HDAC1 overexpression significantly attenuated the proapoptotic effects of testosterone. Additionally, miR-874-3p mimic and inhibitor significantly decreased and increased HDAC1 expression levels, respectively, compared with the control group. miR-874-3p inhibitor failed to attenuate HDAC1 overexpression-induced GC apoptosis. Furthermore, compared with the control group, testosterone treatment notably increased p53 expression and acetylation. Compared with the control group, western blotting analysis showed that miR-874-3p mimic notably increased p53 expression and acetylation, whereas miR-874-3p inhibitor markedly decreased p53 expression and acetylation. However, miR-874-3p inhibitor did not further decrease p53 acetylation and expression in cell overexpressing HDAC1. Collectively, the results of the present study indicated that miR-874-3p was upregulated in PCOS and promoted testosterone-induced GC apoptosis by suppressing HDAC1-mediated p53 deacetylation. Therefore, the present study improved the current understanding of the pathogenesis of PCOS and GC apoptosis.

show abstract

Role of microRNA in the Pathogenesis of Polycystic Ovary Syndrome

Cited by 35 publications

References 64 publications

MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance

MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome

MicroRNA‑874‑3p promotes testosterone‑induced granulosa cell apoptosis by suppressing HDAC1‑mediated p53 deacetylation

Contact Info

Product

Resources

About