Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway

Yang, Dongyong; Wang, Yanqing; Zheng, Y.; Dai, Fangfang; Liu, Shiyi; Yuan, Mengqin; Deng, Zhanfeng; Bao, Anyu; Cheng, Yanxiang

doi:10.1186/s13048-021-00792-2

Cited by 20 publications

(12 citation statements)

References 40 publications

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“…If this chronic inflammation can be attenuated, it will likely have important significance for improving fertility of PCOS patients. Yang et al, in their work silenced UCA1 and inhibited most pathological progression in PCOS, such as preventing pro-inflammation production and promoting GC proliferation (52). So the target for inflammatory is crucial in PCOS therapy.…”

Section: Discussionmentioning

confidence: 99%

The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment

Líu

Fan

et al. 2021

Front. Immunol.

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BackgroundHormones and immune imbalance are critical factors in polycystic ovary syndrome (PCOS). The alternation of immune microenvironment of oocytes may play a significant role in infertility of PCOS patients.ObjectiveThis study explores the role of follicular fluid microenvironment change in inflammatory pathways activation of granulosa cells (GCs) in PCOS women infertility.MethodsWe enrolled 27 PCOS patients and 30 controls aged 22 to 38 years who underwent IVF and collected their luteinized granulosa cells (LGCs). Meanwhile, a granulosa-like tumor cell line (KGN) as a cell-model assisted this study. Key inflammatory markers in human ovarian GCs and follicular fluid were detected by RT-qPCR, Western blotting, or ELISA. The KGN cells were treated with follicle supernatant mixed with normal medium to simulate the microenvironment of GCs in PCOS patients, and the inflammation indicators were observed. The assembly of NLRP3 inflammasomes was detected by immunofluorescence techniques. Dihydroethidium assay and EdU proliferation assay were used to detect ROS and cell proliferation by flow cytometry.ResultsCompared with normal controls (n = 19), IL-1β (P = 0.0005) and IL-18 (P = 0.021) in the follicular fluid of PCOS patients (n = 20) were significantly increased. The NF-κB pathway was activated, and NLRP3 inflammasome was formatted in ovarian GCs of PCOS patients. We also found that inflammation of KGN cells was activated with LPS irritation or stimulated by follicular fluid from PCOS patients. Finally, we found that intracellular inflammation process damaged mitochondrial structure and function, which induced oxidative stress, affected cellular metabolism, and impaired cell proliferation.ConclusionInflammatory microenvironment alteration in the follicular fluid of PCOS patients leads to activated inflammatory pathway in GCs, serving as a crucial factor that causes adverse symptoms in patients. This study provides a novel mechanism in the inflammatory process of PCOS.

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Section: Discussionmentioning

confidence: 99%

The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment

Líu

Fan

et al. 2021

Front. Immunol.

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“…The level of TNF-α in ovarian tissues was determined using a mouse 1). Here, we used TNF-αinduced KGN cells as an in vitro research model to mimic PCOS-related cell injury, which is in line with previous studies [33][34][35]. Cells were seeded in 6-well plates at a density of 1 × 10 5 and cultured in an incubator with 5% CO 2 at 37°C.…”

Section: Quantification Of Tnf-α Il-1β Dhea and Testosteronementioning

confidence: 87%

MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1

Gao

et al. 2021

Bioengineered

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses a great threat to women's health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to establish an in vivo model of PCOS. We found that enhanced activation of NLRP3 inflammasome was accompanied by downregulation of miR-1224-5p in ovarian tissue of PCOS mice. The effect of miR-1224-5p was further explored in TNF-α-treated human granulosa-like tumor (KGN) cells. Upregulation of miR-1224-5p suppressed TNF-α-induced secretion of DHEA and testosterone. MiR-1224-5p attenuated TNF-α-induced inflammation by inhibiting NLRP3 inflammasome activation, IL-1β synthesis, and nuclear factor kappa B (NF-κB) p65 nuclear translocation. Notably, miR-1224-5p decreased the expression of Forkhead box O 1 (FOXO1) and its downstream gene thioredoxin interaction protein (TXNIP). Luciferase reporter assay confirmed FOXO1 as a target of miR-1224-5p. Upregulation of FOXO1 abolished miR-1224-5p-induced activation of NLRP3 inflammasome, demonstrating that miR-1224-5p might inhibit NLRP3 inflammasome activation through regulating FOXO1. This study provided novel insights into the pathogenesis of PCOS and suggested that miR-1224-5p might be a promising target for treating PCOS.

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“…Jiang et al observed a down-regulated of lncRNA HOTAIR could alleviates PCOS ( 43 ). And Yang et al showed that silencing the lncRNA UCA1 could inhibit the development of PCOS via regulating PI3K-AKT signaling pathway ( 44 ). Moreover, downregulating lncRNA NEAT1 could also inhibit apoptosis and improve cell proliferation of ovarian GCs via microRNA-381/IGF1 axis, which associated with improved pathological process of PCOS ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing Profiles About lncRNAs and mRNAs of Ovarian Granulosa Cells in Polycystic Ovary Syndrome

Zheng

Bian

et al. 2021

Front. Med.

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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.

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Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway

Cited by 20 publications

References 40 publications

The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment

The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment

MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1

High-Throughput Sequencing Profiles About lncRNAs and mRNAs of Ovarian Granulosa Cells in Polycystic Ovary Syndrome

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