1. Benzo(a)pyrene promotes the malignant progression of malignant-transformed BEAS-2B cells by regulating YTH N6-methyladenosine RNA binding protein 1 to inhibit ferroptosis.
- Author
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Wang N, Chen HQ, Zeng Y, Shi Y, Zhang Z, Li JY, Zhou SM, Li YW, Deng SW, Han X, Zhou ZY, Yao ML, and Liu WB
- Subjects
- Humans, Cell Line, Cell Transformation, Neoplastic chemically induced, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic drug effects, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic pathology, Reactive Oxygen Species metabolism, Receptors, Transferrin metabolism, Receptors, Transferrin genetics, Amino Acid Transport System y+ metabolism, Amino Acid Transport System y+ genetics, RNA-Binding Proteins metabolism, RNA-Binding Proteins genetics, Lung Neoplasms pathology, Lung Neoplasms metabolism, Lung Neoplasms chemically induced, Lung Neoplasms genetics, Lipid Peroxidation drug effects, Epithelial Cells drug effects, Epithelial Cells metabolism, Epithelial Cells pathology, Phospholipid Hydroperoxide Glutathione Peroxidase metabolism, Phospholipid Hydroperoxide Glutathione Peroxidase genetics, Ferritins, Oxidoreductases, Antigens, CD, Ferroptosis drug effects, Benzo(a)pyrene toxicity, Cell Movement drug effects
- Abstract
Benzo[a]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10 μM BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25 μM) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe
2+ , malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe2+ , MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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