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Communications Biology

Communications Biology

IF: 5.2
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MNT inhibits lung adenocarcinoma ferroptosis and chemosensitivity by suppressing SAT1

Published:3 June 2024 DOI: PMID: 38831092
Guangyin Zhao, Jiaqi Liang, Yuchen Zhang, Guangyao Shan, Yunyi Bian, Jie Gu, Cheng Zhan, Di Ge

Abstract

Ferroptosis, a type of iron-dependent non-apoptotic cell death, plays a vital role in both tumor proliferation and resistance to chemotherapy. Here, our study demonstrates that MAX’s Next Tango (MNT), by involving itself in the spermidine/spermine N1-acetyltransferase 1 (SAT1)-related ferroptosis pathway, promotes the proliferation of lung adenocarcinoma (LUAD) cells and diminishes their sensitivity to chemotherapy. Initially, an RNA-sequence screen of LUAD cells treated with ferroptosis inducers (FINs) reveals a significant increase in MNT expression, suggesting a potential link between MNT and ferroptosis. Overexpression of MNT in LUAD cells hinders changes associated with ferroptosis. Moreover, the upregulation of MNT promotes cell proliferation and suppresses chemotherapy sensitivity, while the knockdown of MNT has the opposite effect. Through the intersection of ChIP-Seq and ferroptosis-associated gene sets, and validation by qPCR and western blot, SAT1 is identified as a potential target of MNT. Subsequently, we demonstrate that MNT binds to the promoter sequence of SAT1 and suppresses its transcription by ChIP-qPCR and dual luciferase assays. Restoration of SAT1 levels antagonizes the efficacy of MNT to inhibit ferroptosis and chemosensitivity and promote cell growth in vitro as well as in vivo. In the clinical context, MNT expression is elevated in LUAD and is inversely connected with SAT1 expression. High MNT expression is also associated with poor patient survival. Our research reveals that MNT inhibits ferroptosis, and impairing chemotherapy effectiveness of LUAD. The transcription factor MNT binds to the SAT1 promoter region and represses its transcription, leading to ferroptosis and chemotherapy resistance in lung adenocarcinoma.

Substances (28)

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
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 295 suppliers $10.00-$4712.50
DEFEROXAMINE MESYLATE 138-14-7 C26H52N6O11S 295 suppliers $10.00-$4712.50

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