Cervical cancer is a significant concern among women, and radioresistance is a key obstacle in its treatment. Ferroptosis is a new way of death, which offers a fresh idea for tumor radiotherapy. We aimed to elucidate the mechanisms of lncRNA-mediated ferroptosis in radiosensitivity of cervical cancer. In this study, TCGA database analysis was used to determine key lncRNAs associated with ferroptosis and radiosensitivity in cervical cancer. The function and mechanism of lncRNAs on ferroptosis and radiosensitivity was investigated by in vitro and in vivo. We found that radiotherapy triggered cervical cancer cell ferroptosis and ferroptosis inducer inhibited the viability of radiotherapy-treated cervical cancer cells. Bioinformatics analysis identified EGFR-AS1 as a lncRNA associated with radiosensitivity and ferroptosis in cervical cancer. EGFR-AS1 was significantly increased in radiotherapy-treated cervical cancer cells and radioresistant tissues. Interfering with EGFR-AS1 expression induced ferroptosis of cervical cancer cells. Animal experiments revealed that EGFR-AS1 inhibits radiosensitivity in vivo. Mechanically, EGFR-AS1 bound to the m6A recognition protein IGF2BP3. Meanwhile, EGFR-AS1 was involved in the p53 signaling pathway and regulated APAF1 through IGF2BP3 and m6A modifications. Furthermore, EGFR-AS1 restrained ferroptosis in cervical cancer cells via the m6A/APAF1 axis. In conclusion, this study revealed that EGFR-AS1 suppressed ferroptosis of cancer cells via the m6A/IGF2BP3/APAF1 axis, thereby decreasing radiosensitivity of cervical cancer. Our study offers fresh ideas for the radiosensitization mechanism of cervical cancer.
Chen et al. (Thu,) studied this question.