ArticleJournal of assisted reproduction and genetics2024
SIRT5 suppresses the trophoblast cell proliferation, invasion, and migration to promote preeclampsia via desuccinylating HOXB3.
Article in Journal of assisted reproduction and genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Elevated BACH1 Contributes to Mitochondrial Succinylome Remodeling and Trophoblast Bioenergetic Dysfunction in Preeclampsia.Antioxidants (Basel, Switzerland) · 2026Article
- Unveiling the importance of SIRT5 for cardiac health and disease in an era of increasing longevity.GeroScience · 2026Review
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
purposePreeclampsia (PE) is a pregnancy-specific syndrome with increasing maternal and perinatal morbidity and mortality. Succinylation, a post-translational modification event, has been found in various diseases. However, the role of succinylation in PE has not been explored. This study aimed to investigate the effect of succinylation on PE and the underlying mechanisms.
methodsThirty-two PE patients and 32 normal pregnancy volunteers were recruited. Human extravasated trophoblast cells (HTR-8/SVneo) were used in in vitro study. RT-qPCR was performed to detect the expression of succinylation-related mRNAs. The cell proliferation, invasion, and migration were assessed using cell counting kit-8, ethynyldeoxyuridine, transwell, and wound healing assays. Co-immunoprecipitation and dual-luciferase reporter assays were performed to analyze the interaction between sirtuin (SIRT)5 and homeobox box 3 (HOXB3).
resultsSIRT5 was increased in the placental tissues of PE patients. SIRT5 inhibition increased cell proliferation, invasion, and migration in HTR-8/SVneo cells. Mechanistic investigations indicated that HOXB3 was a downstream regulatory target of SIRT5-mediated desuccinylation. Rescue experiments further verified that silencing of HOXB3 inhibited cell proliferation, invasion, and migration. Additionally, HOXB3 deficiency reversed the activation of the Notch and β-catenin signaling pathway induced by SIRT5 inhibition.
conclusionSIRT5 inhibited the trophoblast cell proliferation, invasion, and migration to promote PE through suppressing Notch and β-catenin signaling pathway activation via desuccinylating HOXB3.
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