High expression of AlkB homolog 5 suppresses the progression of non‐small cell lung cancer by facilitating ferroptosis through m6A demethylation of SLC7A11

• DOI: 10.1002/tox.24272
• Publication Date: 2024-04-20T10:34:30Z
• Authors: Zhangzhou Huang; Gen Lin; Yaping Hong; Lihong Weng; Kai Zhu; Wu Zhuang
• Keywords: Demethylation; AlkB

Abstract Objective Non‐small cell lung cancer (NSCLC) is a prevailing LC characterized by poor outcomes. AlkB homolog 5 (ALKBH5) functions as tumor suppressor in several cancers. This study delved into the role of ALKBH5 NSCLC development. Methods TCGA database predicted expression patients. levels and human bronchial epithelial cells were determined. pcDNA3.1‐ALKBH5/NC, pcDNA3.1‐SLC7A11/NC, ferrostatin‐1 used to explore interactions among ALKBH5, SLC7A11, ferroptosis. SLC7A11 mRNA its protein measured RT‐qPCR Western blot. Cell viability, apoptosis, migration, invasion assessed CCK‐8, flow cytometry, Transwell. Total N6‐methyladenosine (m6A) quantification enrichment on determined, followed observation Ki67, SLC7A11‐positive numbers. Glutathione (GSH), lipid reactive oxygen species (lipid‐ROS), malondialdehyde (MDA), iron ion contents Animal experiments further analyzed development glutathione peroxidase 4 (GPX4) expression. Results Bioinformatics analysis revealed lowly‐expressed was downregulated upregulation repressed proliferation activity, invasion, facilitated apoptosis. decreased GSH, increased lipid‐ROS, MDA, contents, reducing m6A modification. partly annulled effect overexpression ferroptosis malignant behaviors. In vivo assays elucidated suppression GPX4 levels. Conclusion downregulates transcription decreasing modification, thus promoting ultimately repressing progression.