Characterization of altered microRNAs related to different phenotypes of polycystic ovarian syndrome (PCOS) in serum, follicular fluid, and cumulus cells

Rad, Hanieh Motahari; Mowla, Seyed Javad; Ramazanali, Fariba; Valojerdi, Mojtaba Rezazadeh

doi:10.1016/j.tjog.2022.05.013

Cited by 13 publications

(12 citation statements)

References 72 publications

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“…An apparent dysfunction in ovarian steroidogenesis has been shown to be associated with polycystic ovarian syndrome and plays a crucial role in its prognosis [ 47 , 48 ]. Researchers found that approximately 70% of invasive breast cancers have some degree of independence from the estrogen hormone for cell proliferation and growth [ 49 ], and Keenan et al found that estrogen signaling was independently associated with resistance in hormone-positive breast cancer [ 50 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Tumor Microenvironment Characterization in Breast Cancer Identifies Prognostic Pathway Signatures

Qiu

Han

et al. 2022

Genes

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Breast cancer is one of the most common female malignancies worldwide. Due to its early metastases formation and a high degree of malignancy, the 10 year-survival rate of metastatic breast cancer does not exceed 30%. Thus, more precise biomarkers are urgently needed. In our study, we first estimated the tumor microenvironment (TME) infiltration using the xCell algorithm. Based on TME infiltration, the three main TME clusters were identified using consensus clustering. Our results showed that the three main TME clusters cause significant differences in survival rates and TME infiltration patterns (log-rank test, p = 0.006). Then, multiple machine learning algorithms were used to develop a nine-pathway-based TME-related risk model to predict the prognosis of breast cancer (BRCA) patients (the immune-related pathway-based risk score, defined as IPRS). Based on the IPRS, BRCA patients were divided into two subgroups, and patients in the IPRS-low group presented significantly better overall survival (OS) rates than the IPRS-high group (log-rank test, p < 0.0001). Correlation analysis revealed that the IPRS-low group was characterized by increases in immune-related scores (cytolytic activity (CYT), major histocompatibility complex (MHC), T cell-inflamed immune gene expression profile (GEP), ESTIMATE, immune, and stromal scores) while exhibiting decreases in tumor purity, suggesting IPRS-low patients may have a strong immune response. Additionally, the gene-set enrichment analysis (GSEA) result confirmed that the IPRS-low patients were significantly enriched in several immune-associated signaling pathways. Furthermore, multivariate Cox analysis revealed that the IPRS was an independent prognostic biomarker after adjustment by clinicopathologic characteristics. The prognostic value of the IPRS model was further validated in three external validation cohorts. Altogether, our findings demonstrated that the IPRS was a powerful predictor to screen out certain populations with better prognosis in breast cancer and may serve as a potential biomarker guiding clinical treatment decisions.

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Section: Resultsmentioning

confidence: 99%

Tumor Microenvironment Characterization in Breast Cancer Identifies Prognostic Pathway Signatures

Qiu

Han

et al. 2022

Genes

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“…The concurrent upregulation of ERα expression, along with inflammation, plays a pivotal role in estrogen-induced proliferation by initiating CCND-1 gene transcription and overexpression [ 52 ]. This process contributes to abnormal cell proliferation and disturbances in ovarian follicular development, defining the features of PCOS [ 53 ]. Present study demonstrates VNE supplementation to alleviate the elevated signalling of CCND-1 in PCOS (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mitigation of letrozole induced polycystic ovarian syndrome associated inflammatory response and endocrinal dysfunction by Vitex negundo seeds

Kar,

Sil,

Ghosh

et al. 2024

J Ovarian Res

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Background Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that necessitates effective and safe treatment alternatives. This study aimed to evaluate the therapeutic efficacy of Vitex negundo seed in a letrozole-induced PCOS rat model. Results Findings of the present study demonstrated that administration of hydro-ethanolic extract of Vitex negundo (VNE) effectively restored endocrino-metabolic imbalances associated with PCOS, along with correction of antioxidant enzymes level, proinflammatory cytokines, and apoptotic bio-markers. LC-MS analysis confirmed the presence of cinnamic acid, plumbagin and nigundin B as the prominent phytochemicals in VNE. The observed beneficial effects could be attributed to the active compounds in Vitex negundo extract, which exhibited hypoglycemic, hypolipidemic, and catabolic effects on body weight. Additionally, the extract contributed to hormonal balance regulation by modulating the steroidogenic enzymes, specifically by tuning gonadotropins level and correcting the LH:FSH ratio, through the modulation of ERα signalling and downregulation of NR3C4 expression. The antioxidant properties of phytochemicals in Vitex negundo seed were apparent through the correction of SOD and catalase activity. While it’s anti-inflammatory and antiapoptotic action were associated with the regulation of mRNA expression of TNF-α, IL-6, BAX, Bcl2. Molecular docking study further indicated the molecular interaction of above mentioned active phytocompounds of VNE with ERα, NR3C4 and with TNFα that plays a critical mechanistic gateway to the regulation of hormone signalling as well as synchronizing the inflammation cascade. Furthermore, the histomorphological improvement of the ovaries supported the ameliorative action of Vitex negundo extract in the letrozole-induced PCOS model. Conclusions This study indicates the potential of Vitex negundo seed as a multifaceted therapeutic option for PCOS. VNE offers a holistic strategy for PCOS with antiandrogenic, anti-inflammatory, and antioxidant properties, driven by its major compounds like cinnamic acid, plumbagine, and nigundin B.

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“…It is caused by a disruption of normal ovarian or adrenal function, leading to excessive androgen production. Ovarian miRNA expression profiles in tissue [ 36 ], granulosa cells [ 37 ], cumulus cells [ 25 , 38 ] and follicular fluid [ 25 , 38 , 39 ] have been shown to be altered in women with PCOS. We therefore assumed that serum miRNA profiles alter between phenotypes with HA and phenotype D (no HA), which was not the case in our data set.…”

Section: Discussionmentioning

confidence: 99%

“…Research indicates that levels of circulating miRNAs play an important role in the progression of metabolic diseases [ 20 ], malignancies [ 21 ] and endocrine system disorders [ 22 ]. Several studies have shown that women with PCOS show altered miRNA expression profiles in different cell types and body fluids [ 23 , 24 , 25 , 26 ] such as the ovary [ 27 ], follicular fluid [ 28 ], blood [ 29 ], serum [ 24 ] and adipocytes [ 30 ]. Since extracellular miRNAs are stable in serum, easy to detect and potentially disease-specific, they became ideal biomarkers for various diseases and conditions [ 31 ] including PCOS [ 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…Since extracellular miRNAs are stable in serum, easy to detect and potentially disease-specific, they became ideal biomarkers for various diseases and conditions [ 31 ] including PCOS [ 32 , 33 , 34 ]. Data on miRNA expression in PCOS phenotypes [ 25 , 26 , 35 ] are scarce and have not yet been compared in serum between all four PCOS phenotypes according to the Rotterdam classification. The main aim of this pilot study was to compare the serum expression profiles of 12 miRNAs previously related with PCOS between the four PCOS phenotypes and to analyze them, both as PCOS-specific and in phenotypes with HA.…”

Section: Introductionmentioning

confidence: 99%

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Serum Expression of miR-23a-3p and miR-424-5p Indicate Specific Polycystic Ovary Syndrome Phenotypes: A Pilot Study

Trummer,

Hoeller,

Reintar

et al. 2024

IJMS

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MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a post-transcriptional level. Observational studies suggest an association of serum miRNAs and polycystic ovary syndrome (PCOS), a common heterogeneous endocrinopathy characterized by hyperandrogenism (HA), oligo- or amenorrhea (OM) and polycystic ovaries. It is not known whether these miRNA profiles also differ between PCOS phenotypes. In this pilot study, we compared serum expression profiles between the four PCOS phenotypes (A–D) and analyzed them both in PCOS (all phenotypes) and in phenotypes with HA by quantitative-real-time PCR (qRT-PCR). The serum expression of miR-23a-3p was upregulated in phenotype B (n = 10) and discriminated it from phenotypes A (n = 11), C (n = 11) and D (n = 11, AUC = 0.837; 95%CI, 0.706–0.968; p = 0.006). The expression of miR-424-5p was downregulated in phenotype C (n = 11) and discriminated it from phenotypes A, B and D (AUC = 0.801; 95%CI, 0.591–1.000; p = 0.007). MiR-93-5p expression was downregulated in women with PCOS (all phenotypes, n = 42) compared to controls (n = 8; p = 0.042). Phenotypes with HA (A, B, C; n = 32) did not show differences in the analyzed expression pattern. Our data provide new insights into phenotype-specific miRNA alterations in the serum of women with PCOS. Understanding the differential hormonal and miRNA profiles across PCOS phenotypes is important to improve the pathophysiological understanding of PCOS heterogeneity.

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Characterization of altered microRNAs related to different phenotypes of polycystic ovarian syndrome (PCOS) in serum, follicular fluid, and cumulus cells

Cited by 13 publications

References 72 publications

Tumor Microenvironment Characterization in Breast Cancer Identifies Prognostic Pathway Signatures

Tumor Microenvironment Characterization in Breast Cancer Identifies Prognostic Pathway Signatures

Mitigation of letrozole induced polycystic ovarian syndrome associated inflammatory response and endocrinal dysfunction by Vitex negundo seeds

Serum Expression of miR-23a-3p and miR-424-5p Indicate Specific Polycystic Ovary Syndrome Phenotypes: A Pilot Study

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