Transfer RNA-derived fragments (tRFs) represent a class of non-coding RNAs, typically ranging from 16 to 40 nucleotides in length, and have been implicated in the regulation of oncogenic processes. Despite emerging evidence of their involvement in various malignancies, the role of tRFs in lung adenocarcinoma remains unclear. The aim of this study is to investigate the expression levels, functional role, and molecular mechanisms of tRF-His-GTG-008 in lung adenocarcinoma. tRF-His-GTG-008, a 31-nucleotide fragment derived from the D-loop at the 5′ end of tRNA-His-GTG-1-1, was identified through high-throughput sequencing. Its expression was assessed in lung adenocarcinoma tissues and cell lines (A549, H-1975) using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and its diagnostic utility was evaluated using receiver operating characteristic curve. Functional assays—including cell proliferation, clone formation, migration, and invasion experiments—were conducted following overexpression or knockdown of tRF-His-GTG-008. In vivo tumorigenicity was evaluated using a xenograft model in immunodeficient mice. The potential target gene was predicted using miRanda and TargetScan databases, and its interaction with LATS2 was validated through dual-luciferase reporter assays, RT-qPCR and western blot analysis. tRF-His-GTG-008 was significantly upregulated in lung adenocarcinoma tissues and cell lines (AUC = 0.717). Overexpression of tRF-His-GTG-008 promoted cell proliferation, clone formation, migration, and invasion of A549 and H-1975 cells, whereas knockdown suppressed these oncogenic phenotypes without notable effects on the cell cycle or apoptosis. In vivo, knockdown of tRF-His-GTG-008 resulted in reduced tumor volume and weight, accompanied by decreased expression of Ki-67 and MMP9. Mechanistically, tRF-His-GTG-008 was found to directly bind to the 3’-UTR of the LATS2 gene, leading to its downregulation. tRF-His-GTG-008 is overexpressed in lung adenocarcinoma and demonstrates diagnostic potential. Its oncogenic effects are mediated through direct targeting and suppression of LATS2, indicating its possible utility as a novel therapeutic target in the management of lung adenocarcinoma.
Luo et al. (Wed,) studied this question.