Role of the tRNA-Derived Small RNAs in Cancer: New Potential Biomarkers and Target for Therapy

Noncoding RNAs are untranslated RNA molecules that can be divided into two main types: infrastructural, including transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), and regulatory, including long ncRNAs (lncRNAs) and small ncRNAs (sRNA). Among small ncRNA, the role of microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) in cancer is well documented. Recently, other small ncRNAs have been described. In particular, tRNA-derived small RNAs (tsRNA) have been found to be frequently dysregulated in cancer. Since tsRNAs can be considered unique sequences and are able to bind both Argonaute proteins (like miRNAs) and Piwi proteins (like piRNAs), their dysregulation could play a critical role in cancer by interfering with gene expression regulation at different levels. Like microRNAs, ts-53 (previously known as miR-3676) interacts with the 3'UTR of TCL1, therefore supporting a role for tsRNAs on the posttranscriptional regulation of gene expression. Like piRNAs, tsRNAs are produced as single-stranded molecules and can interact with DNA and histone methylation machinery, suggesting a role in the pretranscriptional regulation of gene expression. Herein, we describe the most recent findings about the role of tsRNAs in cancer.