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ATF1 promotes ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2.
- Source :
-
Experimental cell research [Exp Cell Res] 2024 Sep 01; Vol. 442 (1), pp. 114190. Date of Electronic Publication: 2024 Aug 03. - Publication Year :
- 2024
-
Abstract
- Background: Ferroptotic proteins are promising therapeutic targets for lung cancer. The PROM2 is upregulated in lung cancer and known to suppress ferroptosis. This study examined the molecular mechanisms for PROM2-induced ferroptosis resistance in lung cancer.<br />Methods: Ferroptosis in lung cancer was assessed by iron kit, and transmission electron microscopy was applied to observe the changes in mitochondrial morphology. BODIPY™ was applied to test the lipid ROS, and MeRIP was performed to test the m6A modification of PROM2. RIP assay was employed for confirming the binding between METTL3 and PROM2. In addition, dual luciferase assay was employed for exploring the transcriptional regulation of ATF1 to METTL3, and the binding relation between ATF1 and METTL3 promoter region was explored by ChIP assay.<br />Results: Expression levels of PROM2 were significantly higher in lung cancer cell lines than a noncancerous control line, and PROM2 knockdown significantly reduced both cancer cell viability and proliferation rate. In addition, PROM2 knockdown reduced xenograft tumor growth and exacerbated erastin-induced ferroptosis. Compared to PROM2 mRNA from control cells, transcripts in lung cancer cells exhibited enhanced m6A levels, and showed greater binding with METTL3. Further, ATF1 upregulated METTL3 transcription, thereby stabilizing PROM2 mRNA and increasing ferroptosis resistance.<br />Conclusion: ATF1 could promote ferroptosis resistance in lung cancer through enhancing mRNA stability of PROM2. Thus, our work might shed novel insights on discovering therapeutic strategy for lung cancer.<br />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.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Mice, Nude
Cell Line, Tumor
Cell Proliferation genetics
Methyltransferases genetics
Methyltransferases metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Xenograft Model Antitumor Assays
Mice, Inbred BALB C
A549 Cells
Ferroptosis genetics
Lung Neoplasms genetics
Lung Neoplasms pathology
Lung Neoplasms metabolism
RNA Stability genetics
Gene Expression Regulation, Neoplastic
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 442
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 39098467
- Full Text :
- https://doi.org/10.1016/j.yexcr.2024.114190