Identification of Novel tRNA-Leu-CAA-Derived tsRNAs for the Diagnosis and Prognosis of Diffuse Gliomas

PURPOSE: tsRNA is a type of small non-coding RNA derived from tRNA. Diffuse gliomas are the most common brain tumors. This investigation focused on tsRNA identification and characterization within gliomas. METHODS: The sequences of human tRNA and tsRNAs were taken from GtRNAdb, tRFdb and tRFexplorer databases. Data processing and bioinformatic analysis were performed with R or Python software. The expression of tsRNAs in glioma tissues was analyzed by qRT-PCR assay. RESULTS: With computational approaches, we identified hundreds of tsRNAs with available expression abundance in the glioma datasets, most of them derived from the 3′ end or 5′ end of mature tRNA. Among the tsRNAs derived from tRNA-Leu-CAA, ts-26, tRFdb-3012a, and tRFdb-3012b (tRFdb-3012a/b) were significantly decreased in diffuse gliomas. The clinical survivals of glioma patients with low tsRNA (ts-26, tRFdb-3012a, and tRFdb-3012b) expression were remarkably worse than that of those with high expression. Expression of tRFdb-3012a/b was correlated with IDH mutant status and MGMT promoter mutation in gliomas, and tRFdb-3012a/b and ts-23 tended to be highly expressed in patients with the IDH mutant. The enrichment analysis showed that some tRFdb-3012a/b-related genes were enriched in RNA splicing and processing, the spliceosome pathway and astrocyte molecular signatures. Moreover, the 3′ untranslated region of the RBM43 gene was predicted to contain putative binding sites of tRFdb-3012a/b, ts-26 may directly bind to the 3′ untranslated region of the HOXA13 gene, and the expressions of both RBM43 and HOXA13 were up-regulated in diffuse gliomas. High RBM43 and HOXA13 expressions were significantly associated with poor survival outcome of glioma patients. CONCLUSION: These results suggest that tRNA-Leu-CAA-derived tsRNAs (ts-26, tRFdb-3012a, and tRFdb-3012b) could be explored as diagnostic and prognostic biomarkers for diffuse gliomas, and tRFdb-3012a/b and ts-26 may play an important role in the progression of gliomas, through binding RBM43 and HOXA13, respectively.