Inhibition of FoxO1 alleviates polycystic ovarian syndrome by reducing inflammation and the immune response

Huang, Xiaolan; Luo, Xiangmin; Huang, Suzhen; Chen, Xiaoqing; Qiu, Lingling

doi:10.1007/s10142-024-01284-4

Cited by 2 publications

(1 citation statement)

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“…FOXO1 is known to be involved in stem cell differentiation and inflammation ( 44 – 46 ). A recent study found that inhibition of FOXO1 alleviates the pathological changes and ovarian dysfunction in PCOS rat models by inhibiting the TLR4/NF-κB/NLRP3 pathway to alleviate inflammation and immune responses ( 47 ). Therefore, our findings indicate distinct RNA-editing events in adipose tissue functions among PCOS patients compared to healthy controls suggesting a potential link between adipose tissue dysfunction and inflammation.…”

Section: Discussionmentioning

confidence: 99%

RNA editing landscape of adipose tissue in polycystic ovary syndrome provides insight into the obesity-related immune responses

Chen,

Li,

Gao

et al. 2024

Front. Endocrinol.

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BackgroundPolycystic ovary syndrome (PCOS) is the most common reproductive–endocrine disorder with wide-ranging metabolic implications, including obesity. RNA editing, a post-transcriptional modification, can fine-tune protein function and introduce heterogeneity. However, the role of RNA editing and its impact on adipose tissue function in PCOS remain poorly understood.MethodsThis study aimed to comprehensively analyze RNA-editing events in abdominal and subcutaneous adipose tissue of PCOS patients and healthy controls using high-throughput whole-genome sequencing (WGS) and RNA sequencing.ResultsOur results revealed that PCOS patients exhibited more RNA-editing sites, with adenosine-to-inosine (A-to-I) editing being prevalent. The expression of ADAR genes, responsible for A-to-I editing, was also higher in PCOS. Aberrant RNA-editing sites in PCOS adipose tissue was enriched in immune responses, and interleukin-12 biosynthetic process. Tumor necrosis factor (TNF) signaling, nuclear factor kappa B (NF-κB) signaling, Notch signaling, terminal uridylyl transferase 4 (TUT4), hook microtubule tethering protein 3 (HOOK3), and forkhead box O1 (FOXO1) were identified to be of significant differences. Differentially expressed genes (DEGs) in PCOS adipose tissue were enriched in immune responses compared with controls, and the DEGs between subcutaneous and abdominal adipose tissue were also enriched in immune responses suggesting the important role of subcutaneous adipose tissue. Furthermore, we identified the correlations between RNA editing levels and RNA expression levels of specific genes, such as ataxia–telangiectasia mutated (ATM) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) in inflammation pathways and ATM, TUT4, and YTH N6-methyladenosine RNA-binding protein C2 (YTHDC2) in oocyte development pathway.ConclusionsThese findings suggest that RNA-editing dysregulation in PCOS adipose tissue may contribute to inflammatory dysregulations. Understanding the interplay between RNA editing and adipose tissue function may unveil potential therapeutic targets for PCOS management. However, further research and validation are required to fully elucidate the molecular mechanisms underlying these associations.

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Section: Discussionmentioning

confidence: 99%