Cangfu Daotan Wan alleviates polycystic ovary syndrome with phlegm-dampness syndrome via disruption of the PKP3/ERCC1/MAPK axis

Li, Yuan; Wu, Haicui; Guo, Ying; Wei, Chaofeng; Guan, Lu; Ju, Wenhan; Lian, Fang

doi:10.1186/s13048-023-01200-7

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…As for the function of EIF2AK2 , the MAPK pathway was identified as one of its downstream targets in PCOS. The MAPK pathway was reported to regulate the granulosa cell apoptosis and the production of steroid biosynthesis in PCOS [ 101 – 103 ]. Therefore, the EIF2AK2 -MAPK axis could be an important link between epigenetic variation and PCOS phenotype.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated RNA editing of EIF2AK2 in polycystic ovary syndrome: clinical relevance and functional implications

Kong,

Feng,

Yao

et al. 2024

BMC Med

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Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA editing and PCOS, yet the actual role of RNA editing, its association with clinical features, and the underlying mechanisms remain unclear. Methods Ten RNA-Seq datasets containing 269 samples of multiple tissue types, including granulosa cells, T helper cells, placenta, oocyte, endometrial stromal cells, endometrium, and adipose tissues, were retrieved from public databases. Peripheral blood samples were collected from twelve PCOS and ten controls and subjected to RNA-Seq. Transcriptome-wide RNA-Seq data analysis was conducted to identify differential RNA editing (DRE) between PCOS and controls. The functional significance of DRE was evaluated by luciferase reporter assays and overexpression in human HEK293T cells. Dehydroepiandrosterone and lipopolysaccharide were used to stimulate human KGN granulosa cells to evaluate gene expression. Results RNA editing dysregulations across multiple tissues were found to be associated with PCOS in public datasets. Peripheral blood transcriptome analysis revealed 798 DRE events associated with PCOS. Through weighted gene co-expression network analysis, our results revealed a set of hub DRE events in PCOS blood. A DRE event in the eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2:chr2:37,100,559) was associated with PCOS clinical features such as luteinizing hormone (LH) and the ratio of LH over follicle-stimulating hormone. Luciferase assays, overexpression, and knockout of RNA editing enzyme adenosine deaminase RNA specific (ADAR) showed that the ADAR-mediated editing cis-regulated EIF2AK2 expression. EIAF2AK2 showed a higher expression after dehydroepiandrosterone and lipopolysaccharide stimulation, triggering changes in the downstrean MAPK pathway. Conclusions Our study presented the first evidence of cross-tissue RNA editing dysregulation in PCOS and its clinical associations. The dysregulation of RNA editing mediated by ADAR and the disrupted target EIF2AK2 may contribute to PCOS development via the MPAK pathway, underlining such epigenetic mechanisms in the disease.

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Section: Discussionmentioning

confidence: 99%