ArticleFunctional & integrative genomics2023
Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia.
Article in Functional & integrative genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- USP22 suppresses trophoblast cell necroptosis in preeclampsia by stabilizing KAT2A-mediated histone acetylation at the SFRP1 promoter.Journal of translational medicine · 2026Article
- Reactive oxygen species in fetal growth restriction mechanisms and therapeutic directions (Review).International journal of molecular medicine · 2026Review
- Enrichment of decidual CD11c + CD8 + T cells with altered immune function in early pregnancy loss.Nature communications · 2025Article
- Inhibition of hsa_circ_0003314 contributes to trophoblast cell migration and invasion and inhibits pyroptosis in preeclampsia.Histochemistry and cell biology · 2025Article
- Review
- RHBDF1 promotes PERK expression through the JNK/FoxO3 pathway in breast cancer cells.Acta biochimica et biophysica Sinica · 2024Article
- H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes.Clinical epigenetics · 2024Article
- A stress paradox: the dual role of the unfolded protein response in the placenta.Frontiers in endocrinology · 2024Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase 2 (HDAC2) has been demonstrated to regulate trophoblast behaviors. However, its role in trophoblast pyroptosis remains unknown. This study sought to analyze the molecular mechanism of HDAC2 in trophoblast pyroptosis in PE. Expression levels of HDAC2, forkhead box O3 (FOXO3), and protein kinase R-like endoplasmic reticulum kinase (PERK) in placenta tissues and HTR8/SVneo cells and H3K27ac levels in cells were determined. Levels of IL-1β and IL-18 in placenta tissues were determined, and their correlation with HDAC2 was analyzed. Cell proliferation, migration, and invasion were evaluated, and levels of pyroptosis-associated proteins and cytokines were determined. The enrichments of H3K27 acetylation (H3K27ac) and FOXO3 in the FOXO3/PERK promoter region were determined. HDAC2 was downregulated, and FOXO3, PERK, IL-1β, and IL-18 levels were elevated in PE placenta tissues. In HTR8/SVneo cells, HDAC2 downregulation suppressed cell proliferation, migration, and invasion and increased pyroptosis. HDAC2 erased H3K27ac in the FOXO3 promoter region and repressed FOXO3, and FOXO3 bound to the PERK promoter and increased PERK transcription. Functional rescue experiments revealed that silencing FOXO3 or PERK counteracted HDAC2 downregulation-induced cell pyroptosis. Overall, HDAC2 downregulation enhanced H3K27ac to activate FOXO3 and PERK, leading to the occurrence of trophoblast pyroptosis in PE.
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