Fat mass and obesity-associated protein downregulation enhances N6-methyladenosine methylation and drives ovarian cancer progression.

Ovarian cancer remains a major threat to women's health due to difficulties in early detection and limited treatment options. In this study, we investigate the role of FTO (fat mass and obesity-associated protein), a key demethylase involved in N6-methyladenosine (m6A) RNA modification, in the progression of ovarian cancer. Bioinformatics analysis of public datasets, along with validation in clinical samples, revealed that FTO expression was significantly lower in ovarian cancer tissues compared to normal controls. Functional assays demonstrated that FTO downregulation was associated with enhanced proliferation, migration, and invasion of ovarian cancer cells, which coincide with elevated global m6A methylation levels. Conversely, overexpression of FTO in vitro and in vivo significantly inhibited these tumorigenic phenotypes and suppressed tumor growth in a mouse xenograft model. Mechanistic studies demonstrated that FTO is localized in both the nucleus and cytoplasm and that its tumor-suppressive effects are mediated, at least in part, through modulation of Ki67 expression. Together, these findings highlight FTO as a critical negative regulator of ovarian cancer progression and underscore the potential of targeting m6A methylation pathways as a therapeutic target. This research provides novel insights into the epitranscriptomic regulation of ovarian cancer and lays the groundwork for FTO-based therapeutic development.