1. MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma.
- Author
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Liang J, Bi G, Huang Y, Zhao G, Sui Q, Zhang H, Bian Y, Yin J, Wang Q, Chen Z, and Zhan C
- Subjects
- Humans, Animals, Mice, Cisplatin pharmacology, Cisplatin therapeutic use, Cell Line, Tumor, Cell Proliferation, Cell Cycle, Nuclear Proteins metabolism, Nuclear Proteins therapeutic use, MafF Transcription Factor, Ferroptosis genetics, Adenocarcinoma of Lung drug therapy, Adenocarcinoma of Lung genetics, Adenocarcinoma of Lung radiotherapy, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms radiotherapy
- Abstract
Aims: Lung cancer is the leading cause of cancer mortality and lung adenocarcinoma (LUAD) accounts for more than half of all lung cancer cases. Tumor elimination is mostly hindered by drug resistance and the mechanisms remain to be explored in LUAD., Methods: CRISPR screens in cell and murine models and single-cell RNA sequencing were conducted, which identified MAF bZIP transcription factor F (MAFF) as a critical factor regulating tumor growth and treatment resistance in LUAD. RNA and ChIP sequencing analyses were performed for transcriptional target expression and specific binding sites of MAFF. Functions of MAFF in inhibiting tumor growth and promoting cisplatin or irradiation efficacy were investigated using cellular and xenograft models., Results: Patients with lung adenocarcinoma and reduced MAFF expression had worse clinical outcomes. MAFF inhibited tumor cell proliferation by regulating the expression of SLC7A11, CDK6, and CDKN2C, promoting ferroptosis and preventing cell cycle progression from G1 to S. MAFF also conferred tumor cells vulnerable to cisplatin-based or ionizing radiation treatments. MAFF reduction was a final event in the acquisition of cisplatin resistance of LUAD cells. The intracellular cAMP/PKA/CREB1 pathway upregulated MAFF in response to cisplatin-based or ionizing radiation treatments., Conclusions: MAFF suppresses tumor growth, and pharmacological agonists targeting MAFF may improve cisplatin or irradiation therapies for lung adenocarcinoma patients., 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 Ltd. All rights reserved.)
- Published
- 2024
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