N6-Methyladenosine Methylation Regulator Fto Promotes Oxidative Stress and Induces Cell Apoptosis in Ovarian Cancer

Abstract

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.

Plain language summary

FTO, 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.

Tweetable abstract

N6-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.

Keywords::

• FTO
• m6A methylation regulator
• ovarian cancer
• oxidative stress
• P53 signaling pathway

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0403

Author contributions

J Wu wrote the paper and conceived and designed the experiments; XQ Wang analyzed the data; X Li collected and provided the sample for this study. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This study was funded by Zhejiang Medical and Health Science and Technology Project (2022KY1160). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by the Ethics Committee of Ningbo Women’s and Children’s Hospital and strictly performed according to the Guide for the Care and Use of Laboratory Animals.

Additional information

Funding

This study was funded by Zhejiang Medical and Health Science and Technology Project (2022KY1160). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.