TRF3a-MetCAT Promotes EGFR-Targeted Therapeutic Resistance through the TRIM21-STAT1-C5a Axis in Lung Adenocarcinoma.

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 conferr

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12501432 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature