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Publication : A pro-metastatic tRNA fragment drives aldolase A oligomerization to enhance aerobic glycolysis in lung adenocarcinoma.

First Author  Wang Q Year  2024
Journal  Cell Rep Volume  43
Issue  8 Pages  114550
PubMed ID  39058593 Mgi Jnum  J:353825
Mgi Id  MGI:7716358 Doi  10.1016/j.celrep.2024.114550
Citation  Wang Q, et al. (2024) A pro-metastatic tRNA fragment drives aldolase A oligomerization to enhance aerobic glycolysis in lung adenocarcinoma. Cell Rep 43(8):114550
abstractText  Despite being the leading cause of lung cancer-related deaths, the underlying molecular mechanisms driving metastasis progression are still not fully understood. Transfer RNA-derived fragments (tRFs) have been implicated in various biological processes in cancer. However, the role of tRFs in lung adenocarcinoma (LUAD) remains unclear. Our study identified a tRF, tRF-Val-CAC-024, associated with the high-risk component of LUAD, through validation using 3 cohorts. Our findings demonstrated that tRF-Val-CAC-024 acts as an oncogene in LUAD. Mechanistically, tRF-Val-CAC-024 was revealed to bind to aldolase A (ALDOA) dependent on Q125/E224 and promote the oligomerization of ALDOA, resulting in increased enzyme activity and enhanced aerobic glycolysis in LUAD cells. Additionally, we provide preliminary evidence of its potential clinical value by investigating the therapeutic effects of tRF-Val-CAC-024 antagomir-loaded lipid nanoparticles (LNPs) in cell-line-derived xenograft models. These results could enhance our understanding of the regulatory mechanisms of tRFs in LUAD and provide a potential therapeutic target.
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