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.