ArticleInternational journal of biological sciences2026
FOXO3 upregulates and activates GSDME to trigger myeloma cell pyroptosis.
Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Oxidative stress, aging, metabolism, SIRT1, and the gut microbiota: the neurocardiac basis of cognitive loss.Medical gas research · 2027Review
- IFI27 and BAX are Essential for GSDME-Mediated Myeloma Cell Pyroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chasing the FoxO in Metabolic Disorders: Novel Considerations for Oxidative Stress, Programmed Cell Death, Wnt, and the Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Review
- Osteoarthritis and dementia: contrasting disorders driven by mutual pathways of autophagy, mTOR, GLP-1, AMPK, Wnt, and WISP1.Expert review of clinical pharmacology · 2026Review
- Running out the clock: Circadian rhythm dysfunction in cognitive disease.International review of neurobiology · 2026Review
- Agitation, Alzheimer's disease, and autophagy: mechanistic insights into aging pathways, gut microbiome, and artificial intelligence.Frontiers in immunology · 2026Review
- Dementia, mood disorders, and aging: Bridging new avenues of care through shared biological pathways.Aging advancesArticle
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Authors and funding
13 authors.
Funding
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Abstract
Induction of pyroptosis is considered as a novel strategy for the treatment of multiple myeloma, but the potential targets remain unknown. In the present study, we found that GSDME, a key executor of pyroptosis, is the mostly downregulated pyroptosis-related gene in MM cells and its low expression predicts poor prognosis of MM patients. Out of expectation, GSDME transcription is not markedly affected by epigenetic manners in MM cells. In contrast, GSDME expression is controlled by the transcription factor FOXO3. FOXO3 binds to the two recognition sites and upregulates GSDME. Moreover, FOXO3 specifically upregulates the BNIPL family proteins and activates Caspase-3 and GSDME therefore triggering MM cell pyroptosis. In addition, similar to GSDME, FOXO3 is also downregulated in MM and its restoration suppresses myeloma tumor growth. Furthermore, we found corylin, a flavonoid derived from Psoralea Fructus, activates the transcription of both FOXO3 and GSDME. As expected, corylin displays potent anti-MM activity in association with pyroptosis by upregulating FOXO3 and GSDME. In conclusion, FOXO3 is a novel transcription factor of GSDME. Restoration/activation of the FOXO3/GSDME axis could be a promising novel strategy for the treatment of MM.
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