Knockdown of circ-FURIN suppresses the proliferation and induces apoptosis of granular cells in polycystic ovary syndrome via miR-195-5p/BCL2 axis

Chen, Yongqian; Miao, Jintian; Lou, Ge

doi:10.1186/s13048-021-00891-0

Cited by 13 publications

(9 citation statements)

References 33 publications

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“…This study is the first to identify TNFSF10 as a diagnostic marker of necroptosis in PCOS, and its specific function in the development of PCOS needs to be further investigated. BCL2 has been reported to be involved in the development of PCOS ( 56 ). Also, BCL2 was involved in necroptosis in various diseases ( 57 , 58 ).…”

Section: Discussionmentioning

confidence: 99%

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

Wang,

An,

Huang

et al. 2023

Front. Endocrinol.

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BackgroundPolycystic ovary syndrome (PCOS), a common endocrine and reproductive disorder, lacks precise diagnostic strategies. Necroptosis was found to be crucial in reproductive and endocrine disorders, but its function in PCOS remains unclear. We aimed to identify differentially diagnostic genes for necroptosis (NDDGs), construct a diagnostic model to assess the progression of PCOS and explore the potential therapeutic drugs.MethodsGene expression datasets were combined with weighted gene co-expression network analysis (WGCNA) and necroptosis gene sets to screen the differentially expressed genes for PCOS. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a necroptosis-related gene signatures. Independent risk analyses were performed using nomograms. Pathway enrichment of NDDGs was conducted with the GeneMANIA database and gene set enrichment analysis (GSEA). Immune microenvironment analysis was estimated based on ssGSEA algorithm analysis. The Comparative Toxicogenomics Database (CTD) was used to explore potential therapeutic drugs for NDDGs. The expression of NDDGs was validated in GSE84958, mouse model and clinical samples.ResultsFour necroptosis-related signature genes, IL33, TNFSF10, BCL2 and PYGM, were identified to define necroptosis for PCOS. The areas under curve (AUC) of receiver operating characteristic curve (ROC) for training set and validation in diagnostic risk model were 0.940 and 0.788, respectively. Enrichment analysis showed that NDDGs were enriched in immune-related signaling pathways such as B cells, T cells, and natural killer cells. Immune microenvironment analysis revealed that NDDGs were significantly correlated with 13 markedly different immune cells. A nomogram was constructed based on features that would benefit patients clinically. Several compounds, such as resveratrol, tretinoin, quercetin, curcumin, etc., were mined as therapeutic drugs for PCOS. The expression of the NDDGs in the validated set, animal model and clinical samples was consistent with the results of the training sets.ConclusionIn this study, 4 NDDGs were identified to be highly effective in assessing the progression and prognosis of PCOS and exploring potential targets for PCOS treatment.

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Section: Discussionmentioning

confidence: 99%

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

Wang,

An,

Huang

et al. 2023

Front. Endocrinol.

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“…However, the expression of BAX/BCL2 in human GCs has been shown to be higher in PCOS patients when compared to controls ( 7 , 63 ). Interestingly, BCL2 expression has been proposed to be regulated through the interaction between a circular RNA (circRNA) and a newly proposed miRNA involved in PCOS, miR-195-5p ( 63 ). However, in this current study, miR-195-5p was not identified as a differentially expressed miRNA in any of the comparisons.…”

Section: Discussionmentioning

confidence: 96%

Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles

et al. 2023

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IntroductionThe ovarian follicle consists of the oocyte, somatic cells, and follicular fluid (FF). Proper signalling between these compartments is required for optimal folliculogenesis. The association between polycystic ovarian syndrome (PCOS) and extracellular vesicular small non-coding RNAs (snRNAs) signatures in follicular fluid (FF) and how this relates to adiposity is unknown. The purpose of this study was to determine whether FF extracellular vesicle (FFEV)-derived snRNAs are differentially expressed (DE) between PCOS and non-PCOS subjects; and if these differences are vesicle-specific and/or adiposity-dependent.MethodsFF and granulosa cells (GC) were collected from 35 patients matched by demographic and stimulation parameters. FFEVs were isolated and snRNA libraries were constructed, sequenced, and analyzed.ResultsmiRNAs were the most abundant biotype present, with specific enrichment in exosomes (EX), whereas in GCs long non-coding RNAs were the most abundant biotype. In obese PCOS vs. lean PCOS, pathway analysis revealed target genes involved in cell survival and apoptosis, leukocyte differentiation and migration, JAK/STAT, and MAPK signalling. In obese PCOS FFEVs were selectively enriched (FFEVs vs. GCs) for miRNAs targeting p53 signalling, cell survival and apoptosis, FOXO, Hippo, TNF, and MAPK signalling.DiscussionWe provide comprehensive profiling of snRNAs in FFEVs and GCs of PCOS and non-PCOS patients, highlighting the effect of adiposity on these findings. We hypothesize that the selective packaging and release of miRNAs specifically targeting anti-apoptotic genes into the FF may be an attempt by the follicle to reduce the apoptotic pressure of the GCs and stave off premature apoptosis of the follicle observed in PCOS.

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“…We firstly identified the cytoplasmic location of circ-JA760602 in hypoxia-induced AC16 cells. circRNAs can affect cell apoptosis in various disease models by regulating the expression of apoptosis-related mRNAs (27)(28)(29). Considering the effect of circ-JA760602 on apoptosis, we detected its modulation on the expression of apoptosis-related mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Circ-JA760602 promotes the apoptosis of hypoxia-induced cardiomyocytes by transcriptionally suppressing BCL2

Li¹,

Wang²,

Feng³

et al. 2023

Int. J. Dev. Biol.

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Background: Acute myocardial infarction (AMI) is myocardial necrosis caused by the complete or partial obstruction of a coronary artery. Circular RNAs (circRNAs) have been proven as regulators in the progression of various human diseases, including AMI. However, the role of novel circ-JA760602 in AMI remains unknown. Here, we investigated the role of circ-JA760602 in modulating the apoptosis of hypoxia-induced AMI cell model.Methods: The expression of circ-JA760602 in cardiomyocytes treated with hypoxia was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was measured by cell counting kit-8 (CCK-8) assay. Apoptosis of cardiomyocytes was evaluated by TUNEL assay and flow cytometry analysis. The cellular location of circ-JA760602 was identified through fluorescence in situ hybridization (FISH) assay and subcellular fractionation assay. The downstream molecular mechanism of circ-JA760602 were demonstrated by luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. Rescue assays were performed to demonstrate the effects of BCL2 knockdown on circ-JA760602 silencing-mediated cardiomyocyte apoptosis.Results: Circ-JA760602 expression was elevated after hypoxia treatment. Knockdown of circ-JA760602 enhanced viability but curbed apoptosis of hypoxia-treated AC16 cells. EGR1 and E2F1 could activate BCL2 transcription. Cytoplasmic circ-JA760602 bound with EGR1 and E2F1 to thus inhibit their nuclear translocation. BCL2 knockdown reversed the effects of circ-JA760602 silencing on the apoptosis of hypoxia-treated AC16 cells.Conclusion: Circ-JA760602 promotes hypoxia-induced apoptosis of cardiomyocytes by binding with EGR1 and E2F1 to inhibit the transcriptional activation of BCL2.

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Knockdown of circ-FURIN suppresses the proliferation and induces apoptosis of granular cells in polycystic ovary syndrome via miR-195-5p/BCL2 axis

Cited by 13 publications

References 33 publications

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

Obesity and PCOS radically alters the snRNA composition of follicular fluid extracellular vesicles

Circ-JA760602 promotes the apoptosis of hypoxia-induced cardiomyocytes by transcriptionally suppressing BCL2

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