Screening and validation of tsRNAs associated with lung adenocarcinoma

To explore the roles of transfer RNA-derived small RNAs (tsRNAs) in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.

The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center. The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas (TCGA) database (TCGA-LUAD). The target genes were predicted based on TRFtarget2.0 and tRFTar databases. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) database. In vitro cell proliferation, migration, and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.

Compared with the normal tissues, tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues (log₂FC=4.28, FDR<0.05). High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival (HR=1.565, 95%CI=1.142-2.145, P=0.005). And its overexpression promoted cell proliferation and migration (P<0.001), and invasion (P=0.009) of A549 cells, and up-regulated COL1A1 (P=0.002) and VCAN (P=0.022) significantly in the tRF-19-69M8LOJX overexpression cell model.

tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues. And its high expression is closely associated with poor prognosis. The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.