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Updated: Aug 19, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
IGF2BP3 is an essential N6-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells
Xin Xu1,2, Jiangtao Cui3, Hong Wang4
1Department of Clinical Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China.
Abstract:
A lack of promising targets leads to poor prognosis in patients with lung adenocarcinoma (LUAD). Therefore, it is urgent to identify novel therapeutic targets. The importance of the N6-methyladenosine (m6A) RNA modification has been demonstrated in various types of tumors; however, knowledge of m6A-related proteins in LUAD is still limited. Here, we found that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), an m6A reader protein, is highly expressed in LUAD and associated with poor prognosis. IGF2BP3 desensitizes ferroptosis (a new form of regulated cell death) in a manner dependent on its m6A reading domain and binding capacity to m6A-methylated mRNAs encoding anti-ferroptotic factors, including but not limited to glutathione peroxidase 4 (GPX4), solute carrier family 3 member 2 (SLC3A2), acyl-CoA synthetase long chain family member 3 (ACSL3), and ferritin heavy chain 1 (FTH1). After IGF2BP3 overexpression, expression levels and mRNA stabilities of these anti-ferroptotic factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, and IGF2BP3 were revealed in clinical LUAD specimens, further establishing the essential role of IGF2BP3 in desensitizing ferroptosis. Inducing ferroptosis has been gradually accepted as an alternative strategy to treat tumors. Thus, IGF2BP3 could be a potential target for the future development of new biomaterial-associated therapeutic anti-tumor drugs.
Insights
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung adenocarcinoma by blocking ferroptosis, a cell death pathway. Targeting IGF2BP3 may offer new therapeutic strategies for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- RNA Modifications
Background:
- Lung adenocarcinoma (LUAD) has a poor prognosis due to limited therapeutic targets.
- N6-methyladenosine (m6A) RNA modification is crucial in various cancers, but its role in LUAD is underexplored.
- Identifying novel therapeutic targets is critical for improving LUAD patient outcomes.
Purpose of the Study:
- To investigate the role of m6A reader proteins in LUAD.
- To identify novel therapeutic targets for LUAD based on m6A modification.
- To explore the mechanism by which IGF2BP3 influences ferroptosis in LUAD.
Main Methods:
- Analysis of IGF2BP3 expression in LUAD tissues.
- Investigation of IGF2BP3's interaction with m6A-methylated mRNAs.
- Assessment of IGF2BP3's effect on ferroptosis-related gene expression and stability.
- Correlation analysis between IGF2BP3, SLC3A2, and ACSL3 in clinical LUAD specimens.
Main Results:
- IGF2BP3 is highly expressed in LUAD and linked to poor prognosis.
- IGF2BP3 desensitizes LUAD cells to ferroptosis by stabilizing mRNAs of anti-ferroptotic factors (e.g., GPX4, SLC3A2, ACSL3, FTH1).
- Overexpression of IGF2BP3 sustains the expression and stability of these anti-ferroptotic factors.
- Clinical LUAD specimens show significant correlations between SLC3A2, ACSL3, and IGF2BP3.
Conclusions:
- IGF2BP3 plays a critical role in desensitizing LUAD to ferroptosis.
- IGF2BP3 is a potential therapeutic target for developing novel anti-tumor drugs.
- Targeting IGF2BP3 could offer a new strategy for treating LUAD by inducing ferroptosis.
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