ArticleResearch (Washington, D.C.)2025
tRF3a-MetCAT Promotes EGFR-Targeted Therapeutic Resistance through the TRIM21-STAT1-C5a Axis in Lung Adenocarcinoma.
Article in Research (Washington, D.C.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
2 citing papers in PubMed.
- Nano-Enabled Fluorescence Switching: A Novel Strategy for PDGFRβ Detection and TKI Therapy Monitoring.Research (Washington, D.C.) · 2026Article
- Identification of a Highly Potent Neutralizing Nanobody Against Human Adenovirus Type 4.Vaccines · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the effectiveness of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in treating lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations, many patients eventually stop responding to therapy. This resistance typically arises when bypass signaling pathways become activated, undermining the treatment's efficacy. The function of transfer-RNA-derived small RNAs, a novel class of regulatory noncoding RNAs, is poorly understood in EGFR-TKI resistance. This study demonstrates that osimertinib-resistant lung cancer organoid models with EGFR mutations (19del or L858R) exhibit marked up-regulation of tRF3a-MetCAT, which correlates with poor prognosis. tRF3a-MetCAT promotes lung cancer cell proliferation, migration, and invasion in vitro while conferring osimertinib resistance. Mechanistically, tRF3a-MetCAT attenuates the interaction between the E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) and signal transducer and activator of transcription 1 (STAT1), resulting in STAT1 stabilization and transcriptional up-regulation of the downstream target C5. Elevated C5a levels subsequently activate the extracellular signal-regulated kinase signaling pathway, contributing to drug resistance. In vivo, treatment with the C5a-targeting inhibitor eculizumab or the C5a receptor inhibitor PMX53 effectively mitigates tRF3a-MetCAT-induced osimertinib resistance. These results reveal novel resistance pathways in EGFR-mutant lung cancer and suggest therapeutic approaches to addressing EGFR-TKI resistance.
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Registered trials
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