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BMC Biology

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KLF13 promotes ferroptosis and chemosensitivity in lung adenocarcinoma

Published:1 July 2025 DOI: 10.1186/s12915-025-02303-x PMID: 40597044
Haochun Shi,?Binyang Pan,?Gujie Wu,?Jiaqi Liang,?Yunyi Bian,?Guangyao Shan,?Shencheng Ren,?Guoshu Bi,?Cheng Zhan,?Weigang Guo

Abstract

Background: Ferroptosis, a form of cell death reliant on iron metabolism dysregulation and lipid peroxidation, has emerged as a promising target for improving tumor drug resistance. This study aims to unveil the underlying molecular mechanisms of Kruppel-like factor 13 (KLF13) in ferroptosis and chemotherapy sensitivity in lung adenocarcinoma (LUAD).

Results: We conducted RNA sequencing on lung adenocarcinoma cells treated with ferroptosis inducers and found that the expression level of KLF13 changed during ferroptosis, suggesting its potential involvement in this process. Subsequently, we generated stable cell lines overexpressing and knocking down KLF13. Cytotoxicity assays and reactive oxygen species (ROS) detection demonstrated that overexpression of KLF13 promoted ferroptosis induced by IKE and RSL3 in LUAD cells, whereas silencing KLF13 inhibited ferroptosis. Furthermore, overexpression of KLF13 enhanced the chemotherapeutic efficacy of cisplatin and pemetrexed. RNA-seq, qPCR, and western blot experiments revealed that KLF13 downregulated the RNA and protein expression of GPX4. ChIP assays and dual-luciferase reporter gene assays indicated that KLF13 directly bound to the promoter region of GPX4, inhibiting transcriptional activity of GPX4. Additionally, overexpression and knockdown of GPX4 could reverse the effects of KLF13 on ferroptosis and chemosensitivity. These findings were further confirmed through immunohistochemical staining and animal experiments.

Conclusions: Our study reveals that KLF13 promotes ferroptosis in LUAD by inhibiting GPX4, thereby enhancing sensitivity to chemotherapy drugs. Overall, targeting KLF13 may contribute to developing new therapeutic strategies for LUAD.

Substances (34)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Cisplatin 15663-27-1 Cl2H6N2Pt 923 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 Cl2H6N2Pt 923 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 Cl2H6N2Pt 923 suppliers $14.00-$7570.00
Cisplatin 15663-27-1 Cl2H6N2Pt 923 suppliers $14.00-$7570.00
Pemetrexed disodium hemipentahydrate 357166-30-4 C20H24N5NaO7 301 suppliers $18.00-$1208.70
Pemetrexed disodium hemipentahydrate 357166-30-4 C20H24N5NaO7 301 suppliers $18.00-$1208.70
Pemetrexed disodium hemipentahydrate 357166-30-4 C20H24N5NaO7 301 suppliers $18.00-$1208.70
Pemetrexed disodium hemipentahydrate 357166-30-4 C20H24N5NaO7 301 suppliers $18.00-$1208.70
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 286 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 286 suppliers $16.00-$2691.10

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