Integrated Transcriptomic and Functional Profiling Reveals IL-7R/FOXO1 Axis as a Target of Momordicine I in Meningioma
Ying Kao, Jia-Rong Hu, Fu-Chi Yang, Dueng-Yuan Hueng, Chia-Kuang TsaiIntroduction:
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.