METTL3-mediated m6A modification contributes to anlotinib resistance in osteosarcoma by regulating ferroptosis via the circFAM120B/miR-330-3p/PRKDC axis - PubMed
5 hours ago
- #drug-resistance
- #osteosarcoma
- #ferroptosis
- METTL3-mediated m6A modification contributes to anlotinib resistance in osteosarcoma.
- Anlotinib triggers ferroptosis in osteosarcoma cells by suppressing the VEGFR2/STAT3/GPX4 signaling cascade.
- DNA-PKcs (encoded by PRKDC) interacts with IGF1R and activates the IGF1R/STAT3/GPX4 pathway, inhibiting ferroptosis.
- circFAM120B acts as a molecular sponge for miR-330-3p, leading to PRKDC upregulation.
- METTL3 enhances circFAM120B stability via YTHDF1-dependent recognition and promotes its expression.
- METTL3 also facilitates YTHDF2-mediated degradation of pri-miR-330, reducing mature miR-330-3p.
- In vivo studies show METTL3 overexpression increases anlotinib resistance, countered by circFAM120B knockdown or miR-330-3p overexpression.
- STAT3 may contribute to anlotinib resistance through additional pathways like apoptosis, autophagy, and immune evasion.
- The study offers potential targets for overcoming therapeutic resistance in osteosarcoma.