N6-methyladenosine methylation regulator FTO promotes oxidative stress and induces cell apoptosis in ovarian cancer

Aims: This study aimed to reveal the possible molecular mechanism of n6-methyladenosine (m6A) methylation regulator FTO in the biological activities of ovarian cancer (OC) based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases. Materials & methods: A risk score model was constructed to predict the prognosis of patients with OC. The key m6A methylation regulator was screened out based on OC-related microarray datasets. Results: 22 m6A methylation regulators were differentially expressed and interacted with each other in OC. FTO, a key m6A methylation regulator, was singled out. In vivo experiments verified that FTO promoted oxidative stress and apoptosis of OC cells to inhibit tumor growth in nude mice. Conclusion: This study highlighted the tumor-suppressive mechanism of m6A methylation regulator FTO in OC. Tweetable abstractN6-methyladenosine methylation is an emerging epigenetic modification in oncology. This study highlights the involvement of n6-methyladenosine methylation regulator FTO in promoting the stress response and apoptosis of ovarian cancer cells, resulting in the inhibition of ovarian cancer growth. Plain language summaryFTO, an n6-methyladenosine (m6A) demethylase, is involved in tumor progression and metastasis in many cancers, but its role in ovarian cancer (OC) is still unclear. According to analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases, 22 m6A methylation regulators were differentially expressed in OC. The prognosis of OC patients could be predicted by a prognostic risk assessment model. As a key m6A methylation regulator, FTO affected OC prognosis by regulating oxidative stress response and the P53 signaling pathway. Overexpression of FTO inhibited tumor growth in nude mice by facilitating the oxidative stress response and apoptosis of OC cells via activation of the P53 signaling pathway. These findings have implications for prognosis and therapeutic responses, revealing novel potential prognostic biomarkers and providing potential novel targets for anticancer therapy.