Knockdown of lncRNA EGFR-AS1 promotes autophagy-mediated ferroptosis in cervical cancer via regulating EGFR expression through miR-133b

• Published in: Molecular & cellular toxicology Vol. 20; no. 1; pp. 139 - 147
• Main Authors: Dong, Chunlin, Dong, Ruofan, Song, Jing, Yu, Chunqing, Zhuang, Yongju, Guo, Qu
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 2024; Springer Nature B.V
• Subjects: Autophagy; Biomedical and Life Sciences; Cell Biology; Cell viability; Cervical cancer; Chloroquine; Epidermal growth factor receptors; Ferroptosis; Iron; Life Sciences; Non-coding RNA; Nutrient deficiency; Original Article; Overexpression; Pharmacology/Toxicology; Ferroptosis; miR-133b; Autophagy; EGFR; Cervical cancer; EGFR-AS1
• ISSN: 1738-642X; 2092-8467
• DOI: 10.1007/s13273-023-00332-7

Background Autophagy-mediated ferroptosis is implicated in pathogenesis of cancer, including cervical cancer. LncRNAs are involved in regulation of autophagy-mediated ferroptosis. LncRNA EGFR-AS1 stimulates cell growth of cervical cancer, while its role in autophagy-mediated ferroptosis remains unclear. Objectives The aim of this study is to investigate the effect of EGFR-AS1 on autophagy-mediated ferroptosis of cervical cancer, and assess the downstream target of EGFR-AS1. Results The expression of EGFR-AS1 was elevated in cervical cancer tissues, and predicted poor survival rate in patients with cervical cancer. Knockdown of EGFR-AS1 enhanced fluorescence of LC3 in cervical cancer cells. Moreover, protein expression of p62 was decreased, while LC3-II/LC-I ratio was increased by silence of EGFR-AS1. Treatment with lysosomal inhibitor, chloroquine diphosphate salt (CQ) increased p62 expression and LC3-II accumulation in cervical cancer cells with EGFR-AS1 deficiency. Loss of EGFR-AS1 increased cellular iron and ROS level in cervical cancer cells. Furthermore, MDA was increased while SOD was decreased in EGFR-AS1-deficient cells. However, treatment with CQ attenuated EGFR-AS1 deficiency-induced decrease of SOD, increase of MDA, ROS, and cellular iron. Cell viability of cervical cancer was decreased by silence of EGFR-AS1. Loss of EGFR-AS1 increased miR-133b expression to reduce EGFR expression. Over-expression of EGFR weakened EGFR-AS1 deficiency-induced decrease of SOD, increase of MDA, ROS, and cellular iron. Moreover, EGFR-AS1 deficiency-induced increase of LC3-II and decrease of p62 were reversed by over-expression of EGFR. Conclusion Knockdown of EGFR-AS1 promoted autophagy-mediated ferroptosis of cervical cancer via down-regulation of miR-133b-mediated EGFR expression.