IGF2BP3通过PPARγ失调促进膀胱癌肌层浸润的分子机制研究

Abstract

Bladder cancer (BC) is a common urinary-tract malignancy that, once it progresses to the muscle‐invasive form (MIBC), adopts a markedly more aggressive behavior and is linked to significantly poorer patient outcomes. Despite extensive investigation, the molecular drivers of MIBC progression have yet to be fully elucidated. In this study, we demonstrate that IGF2BP3 is markedly upregulated, whereas PPARγ is significantly downregulated, in MIBC tissues compared with non–muscle–invasive disease, and that these reciprocal expression changes correlate with enhanced muscle invasion and adverse clinical outcomes. Comprehensive in vitro analyses reveal that elevated IGF2BP3 modulates BC cell motility, with overexpression enhancing migration and invasion and knockdown reducing these processes, while effects on proliferation and apoptosis were minimal. Mechanistic investigations further indicate that IGF2BP3 manipulation in vitro modulates PPARγ mRNA levels and PPARγ knockdown or overexpression respectively augments or abrogates IGF2BP3‐driven cell motility. Collectively, our findings define a novel IGF2BP3/PPARγ signaling axis that contributes to the aggressive behavior of MIBC and suggest that targeting this pathway may offer new avenues for therapeutic intervention.