ArticleCell death & disease2025
TRIM21-mediated METTL3 degradation promotes PDAC ferroptosis and enhances the efficacy of Anti-PD-1 immunotherapy.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- METTL3 in esophageal cancer: Current insights into molecular mechanisms, subtype heterogeneity and targeted therapy prospects (Review).International journal of oncology · 2026Review
- The Role of NMedComm · 2026Review
- Circ-0030167/IGF2BP1 Induces Mitophagy-Mediated Ferroptosis via HMOX1 mRNA Stabilization in Pancreatic Cancer.Cancer science · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- RM2Target v2.0: an updated database for the target genes of writers, erasers, and readers of RNA modifications.Nucleic acids research · 2026Article
- TRIM family proteins: dual roles in tumor immunity.Frontiers in cell and developmental biology · 2026Review
- TRIM21 suppresses uterine corpus endometrial carcinoma progression by promoting K48 -linked ubiquitination and degradation of SOAT1.Frontiers in immunology · 2026Article
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Bidirectional regulation of the ubiquitin-RNA modification axis in cancer.Frontiers in oncology · 2026Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- METTL3/RBM15 augments the stability of Kdm6b mRNA and promotes STAT1-mediated macrophage activation and atherosclerosis.Experimental & molecular medicine · 2025Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer remains the most lethal human malignancy with limited clinical benefits from currently available anticancer treatments. Ferroptosis has recently attracted great attention as a potential antineoplastic strategy. However, the study of ferroptosis in PDAC remains insufficient. This study revealed that Methyltransferase like 3 (METTL3), as a key oncogenic factor, is frequently upregulated and inhibits ferroptosis by stabilizing SLC7A11 mRNA in PDAC. In addition, we identified a novel post-translational modification of METTL3 and characterized specific regulatory mechanisms of METTL3 protein degradation. The E3 ligase TRIM21 mediated K48-linked polyubiquitination of METTL3 at the K459 site, leading to the proteasomal degradation of METTL3, which prevented tumor progression by promoting ferroptosis. Interestingly, the TRIM21-METTL3 axics mediated ferroptosis effectively increased the expression of immune checkpoint PD-L1 and strengthened antitumor immunity in pancreatic cancer. Together, our findings first elucidated the detailed molecular mechanism of METTL3 degradation and revealed the pivotal role of the TRIM21-METTL3 axis in regulating ferroptosis and antitumor immunity, which may serve as a potential target for pancreatic cancer treatment.
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