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Communications Biology

Communications Biology

IF: 5.2
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KLF11 regulates lung adenocarcinoma ferroptosis and chemosensitivity by suppressing GPX4.

Published:29 May 2023 DOI: 10.1038/s42003-023-04959-z PMID: 37248295
Guangyin Zhao, Jiaqi Liang, Guangyao Shan, Jie Gu, Fengkai Xu, Chunlai Lu, Teng Ma, Guoshu Bi, Cheng Zhan, Di Ge

Abstract

Ferroptosis, an iron-dependent non-apoptotic cell death, has been shown to play a vital role in tumor proliferation and chemotherapy resistance. Here, we report that KLF11 inhibits lung adenocarcinoma (LUAD) cell proliferation and promotes chemotherapy sensitivity by participating in the GPX4-related ferroptosis pathway. Through an RNA-sequence screen from LUAD cells pretreatment with ferroptosis inducers (FINs), we discovered that KLF11 expression was significantly higher in FINs-treated cells, suggesting that KLF11 may be involved in ferroptosis. Overexpression of KLF11 promoted LUAD cells to undergo ferroptosis alterations. Meanwhile, upregulation of KLF11 expression also inhibited cell proliferation and increased chemosensitivity, whereas knockout of KLF11 did the opposite. With ChIP-Seq and RNA-Seq, we identified GPX4 as a downstream target of KLF11. Through ChIP-qPCR and dual luciferase assay, we clarified that KLF11 binds to the promoter region of GPX4 and represses its transcription. Restored GPX4 expression antagonized the ability of KLF11 to promote ferroptosis, increase chemotherapy sensitivity and inhibit cell proliferation in vitro and in vivo. Clinically, KLF11 declined in LUAD and its low expression was associated with reduced patient survival. Our findings established the function of KLF11 to promote ferroptosis in LUAD, thereby inhibiting cell proliferation and enhancing the efficacy of chemotherapy. KLF11 inhibits lung adenocarcinoma cell proliferation and promotes chemotherapy sensitivity by repressing transcription of GPX4 and promoting ferroptosis.

Substances (16)

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
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
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 295 suppliers $10.00-$4712.50
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 295 suppliers $10.00-$4712.50
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
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 249 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 249 suppliers $10.00-$2822.00

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