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Background <p>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.</p> Methods <p>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 <i>in vivo</i>.</p> Results <p>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 <i>in vivo</i>. 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.</p> Conclusions <p>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.</p>

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LncRNA EGFR-AS1 inhibits ferroptosis to reduce radiosensitivity of cervical cancer through the m6A/IGF2BP3/APAF1 axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月5日

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  • Xianglong Chen,
  • Jingyu Li,
  • Yujie Sun,
  • Zhaoyu Ye,
  • Man Long,
  • Junguo Bu,
  • Zirong Fan,
  • Zhaojing Jiang

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.