ArticleMolecular medicine (Cambridge, Mass.)2022
A novel role of FoxO3a in the migration and invasion of trophoblast cells: from metabolic remodeling to transcriptional reprogramming.
Article in Molecular medicine (Cambridge, Mass.), 2022. 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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8 citing papers in PubMed, 17 citations in OpenAlex.
- Estradiol-17β, a key embryonic signal, regulates gene expression and cellular functions in the porcine trophoblast.Biology of reproduction · 2026Article
- Excess backfat deposition and restricted feeding in gestating sows: An overview of mechanisms compromising their health and performance, and regulatory effects of functional dietary fibers.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- The molecular pathogenesis of placenta accreta spectrum disorder and its clinical applications.Archives of gynecology and obstetrics · 2025Review
- Placental whole transcriptome expression profile in patients with early-onset, late-onset preeclampsia and gestational diabetes mellitus.Scientific reports · 2025Article
- Article
- Circulating extracellular vesicle-derived miR-1299 disrupts hepatic glucose homeostasis by targeting the STAT3/FAM3A axis in gestational diabetes mellitus.Journal of nanobiotechnology · 2024Article
- FOXO3a-regulated arginine metabolic plasticity adaptively promotes esophageal cancer proliferation and metastasis.Oncogene · 2024Article
- Calcium/calmodulin dependent protein kinase IV in trophoblast cells under insulin resistance: functional and metabolomic analyses.Molecular medicine (Cambridge, Mass.) · 2023Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development.
methodsLentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC-MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed.
resultsWe found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells.
conclusionsOur results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress.
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