Plasma <scp>tsRNA</scp> Signatures Serve as a Novel Biomarker for Bladder Cancer

Bladder cancer (BLCA) is one of the most common tumors of the urinary tract. The diagnosis of BLCA is mostly by invasive tests, which are damaging and unsuitable for early screening. Current non-invasive diagnostic modalities are insufficient in sensitivity and specificity. Therefore, novel diagnostic markers are urgently needed to facilitate early detection of bladder cancer. tRNA-derived small RNAs (tsRNAs) are considered to be novel and potentially biologically functional non-coding RNAs (ncRNAs). tsRNAs have been used to help early diagnosis of a variety of tumors. However, whether tsRNAs in BLCA are altered or involved in BLCA progression or regulation remains unclear. Here, we identified a group of up-regulated tsRNAs in BLCA by sequencing tsRNAs in the plasma of BLCA patients and normal controls and further screened two highly correlated tsRNAs with BLCA in the training set and validation set, which were named as tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2. ROC analyses of the expression profiles of these two tsRNAs by the validation set identified a high diagnostic value. We also found that circulating tRF-1:28-chrM.Ser-TGA and tiRNA-1:34-Glu-CTC-1-M2 were specifically expressed and released by BLCA cells and were positively correlated with the degree of disease malignancy. In vitro and in vivo experiments revealed that the two tsRNAs exacerbated BLCA progression and played a role in promoting tumor lipid metabolism. Our study screened two plasma tsRNAs that could serve as valuable early screening and diagnostic biomarkers for BLCA and is also expected to provide potential novel molecular targets for the treatment of BLCA.