Integrated Transcriptomic and Functional Profiling Reveals IL-7R/FOXO1 Axis as a Target of Momordicine I in Meningioma.
TL;DR
Results support its development as a novel therapeutic candidate for malignant meningioma treatment and suggest that Momordicine I exerts its antitumor activity through coordinated suppression of cell survival pathways, modulation of cell cycle regulators, and mitochondrial dysfunction.
Abstract
INTRODUCTION Meningiomas are common intracranial tumors lacking effective chemotherapeutic options. Momordicine I, a triterpenoid isolated from bitter melon, has demonstrated anticancer activity, but its effects on meningioma remain unclear. The effect of Momordicine I on meningiomas is studied in this research.
Methods
Human meningioma cells (IOMM-Lee and patient-derived P9) were treated with momordicine I. Cell viability, colony formation, migration, apoptosis, and cell cycle progression were assessed. RNA sequencing, qRT-PCR, Western blotting, and Seahorse analysis were used to investigate molecular mechanisms.
Results
Momordicine I inhibited cell proliferation, colony formation, and migration, while inducing apoptosis and G1/G2-M phase arrest. Transcriptomic analysis revealed downregulation of IL7R, FOXO1, and PLK2. Treatment also increased γ-H2AX and reduced Survivin and Bcl-xL expression, indicating apoptosis via DNA damage and survival signaling suppression. Furthermore, mitochondrial oxidative phosphorylation was impaired.
Discussion
These findings suggest that Momordicine I exerts its antitumor activity through coordinated suppression of cell survival pathways, modulation of cell cycle regulators, and mitochondrial dysfunction. Downregulation of IL7R and FOXO1, both associated with tumor progression and survival, underscores the potential of Momordicine I as a multi-pathway therapeutic agent.
Conclusion
Momordicine I demonstrates potent anti-meningioma effects by targeting the IL7R/FOXO1 axis, inducing apoptosis, and impairing mitochondrial metabolism. These results support its development as a novel therapeutic candidate for malignant meningioma treatment.