Follicle‐stimulating hormone regulates glycolysis of water buffalo follicular granulosa cells through AMPK/SIRT1 signalling pathway

Pan, Yu; Zhu, Jianzong; Lv, Qiao; Shi, Deshun; Yang, Sufang; Xing, Qinghua; Zhang, Ruimen; Cheng, Juanru; Deng, Yanfei

doi:10.1111/rda.14039

Cited by 10 publications

(4 citation statements)

References 41 publications

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“…Thus, glycolysis of GCs is crucial for the follicular development of PCOS. At present, studies on the regulatory factors of glycolysis in GCs mainly focus on endocrine hormones, signalling pathways and nonfollicular fluid miRNAs [ 20 – 22 ]. To the best of our knowledge, the regulation of glycolysis in GCs by FF-derived exosomal miRNAs has not yet been studied.…”

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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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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“…SIRT1 overexpression signi cantly promoted the transcriptional activity and expression of GLUT1, therefore, promoting the cell proliferation and glycolysis in bladder cancer cells [36]. In addition, AMPK/SIRT1 pathway also plays a signi cant role in the regulation of follicle-stimulating hormone on glycolysis in follicular granulosa cells, activation of SIRT1 increased the expression level of glycolytic key proteins and lactic acid production, whereas inhibition of SIRT1 demonstrated the opposite effect [37]. Since SIRT1 acts as a key metabolic sensor in cells and regulates both glucose and lipid metabolism in various tissues, then we try to explore the link between TIMELESS and SIRT1.…”

Section: Discussionmentioning

confidence: 99%

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinomas

Chen,

Han,

Zhang

et al. 2023

Preprint

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Background Oral squamous cell carcinoma (OSCC) is the most common malignant of the oral cavity, with a high prevalence and a poor survival rate. There have been studies that indicate circadian disruption has been related to many biological processes within the body and contributes to different diseases, including cancer. Circadian gene TIMELESS is strongly expression-specific in various tumors, but there are very few studies on TIMELESS and OSCC in the literature. The goal of this research is to inquire the impact of TIMELESS on cell growth and glucose metabolism in OSCC. Methods Expression of TIMELESS in OSCC cell lines and tissues was analyzed by western blot, immunohistochemical (IHC) staining, quantitative real-time PCR (qRT-PCR), TCGA (The Cancer Genome Atlas) and CCLE (Cancer Cell Line Encyclopedia) databases. To evaluate the role of TIMELESS in OSCC, the clone formation experiment, MTS assay, cell cycle assay, EdU experiment and subcutaneous tumor formation experiment in nude mice were employed to detect the cell proliferation. Changes in glucose metabolism phenotype were evaluated by glucose uptake, lactate production, oxygen consumption and medium pH to determine if the phenotypes were linked to TIMELESS, the effect of TIMELESS on SIRT1, HK2, PKM2, GLUT1 and LDHA was also examined. Results Our results demonstrated that the obvious elevation of TIMELESS in OSCC tissues and cell lines, high expression of TIMELESS was conferred shorter overall survival of patients. TIMELESS overexpression promoted OSCC cells proliferation, increased glucose uptake and lactate production, decreased oxygen consumption rate and pH. Whereas the knockdown of TIMELESS remarkably inhibited OSCC cell proliferation both in vitro and in vivo, reduced glucose uptake and lactate production, increased oxygen consumption rate and pH, while overexpression of SIRT1 showed a reversed trend. Correlation analysis demonstrated that expression of SIRT1 was positively associated with TIMELESS expression, and the expression of SIRT1, HK2, PKM2, GLUT1 and LDHA could change with the variation of TIMELESS in OSCC cells. Conclusion TIMELESS promotes OSCC cell growth by promoting glycolysis and inhibiting oxidative phosphorylation through SIRT1.

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“…Glucose is metabolized through the glycolytic pathway, pentose phosphate pathway (PPP), HBP, and polyol pathway [ 23 ]. Among the four identified metabolic pathways, glycolysis accounts for a great proportion of glucose metabolism in GCs [ 44 ]. Glycolysis-related proteins were upregulated in GCs during the primordial-to-primary follicle transition, indicating glycolytic activity in GCs is vital for the development of growing follicles.…”

Section: Discussionmentioning

confidence: 99%

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine

Wang

Feng

Sun

et al. 2022

IJMS

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O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.

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Follicle‐stimulating hormone regulates glycolysis of water buffalo follicular granulosa cells through AMPK/SIRT1 signalling pathway

Cited by 10 publications

References 41 publications

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

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

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinomas

Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine

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