The Role of tRNA-Centered Translational Regulatory Mechanisms in Cancer

Cancer is a leading cause of morbidity and mortality worldwide. While numerous factors have been identified as contributing to the development of malignancy, our understanding of the mechanisms involved remains limited. Early cancer detection and the development of effective treatments are therefore critical areas of research. One class of molecules that play a crucial role in the transmission of genetic information are transfer RNAs (tRNAs), which are the most abundant RNA molecules in the human transcriptome. Dysregulated synthesis of tRNAs directly results in translation disorders and diseases, including cancer. Moreover, various types of tRNA modifications and the enzymes responsible for these modifications have been implicated in tumor biology. Furthermore, alterations in tRNA modification can impact tRNA stability, and impaired stability can prompt the cleavage of tRNAs into smaller fragments known as tRNA fragments (tRFs). Initially believed to be random byproducts lacking any physiological function, tRFs have now been redefined as non-coding RNA molecules with distinct roles in regulating RNA stability, translation, target gene expression, and other biological processes. In this review, we present recent findings on translational regulatory models centered around tRNAs in tumors, providing a deeper understanding of tumorigenesis and suggesting new directions for cancer treatment.