IGF2BP3 promotes epithelial ovarian cancer progression by regulating FASN expression

Ovarian cancer (OC) is the most lethal disease among female reproductive system tumors, particularly epithelial ovarian cancer (EOC). N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and is involved in gene expression regulation. In OC, high expression of the m6A reader protein IGF2BP3 predicts a poor prognosis, but the target molecules and mechanisms underlying this association remain unclear. This study demonstrates that IGF2BP3 promotes EOC progression by recognizing and stabilizing m6A-modified FASN mRNA, thereby activating the WNT/β-catenin signaling pathway. This activation enhances lipid synthesis, increases mitochondrial membrane potential, shortens S-phase duration, and promotes cell proliferation and metastasis. Mechanistically, IGF2BP3 binds to m6A-modified FASN mRNA to enhance its stability, and pharmacological inhibition of FASN by orlistat reverses IGF2BP3-mediated oncogenic effects and WNT/β-catenin activation. In vivo and in vitro experiments confirm that knocking down either IGF2BP3 or FASN reverses these malignant phenotypes. These findings highlight a novel m6A-dependent IGF2BP3–FASN–WNT axis that drives EOC progression, providing a potential biomarker for targeted therapy.