tRNA Function and Dysregulation in Cancer

Abstract

Transfer RNA (tRNA) is a central component of protein synthesis and plays important roles in epigenetic regulation of gene expression in tumors. tRNAs are also involved in many cell processes including cell proliferation, cell signaling pathways and stress response, implicating a role in tumorigenesis and cancer progression. The complex role of tRNA in cell regulation implies that an understanding of tRNA function and dysregulation can be used to develop treatments for many cancers including breast cancer, colon cancer, and glioblastoma. Moreover, tRNA modifications including methylation are necessary for tRNA folding, stability, and function. In response to certain stress conditions, tRNAs can be cleaved in half to form tiRNAs, or even shorter tRNA fragments (tRF). tRNA structure and modifications, tiRNA induction of stress granule formation, and tRF regulation of gene expression through the repression of translation can all impact a cell’s fate. This review focuses on how these functions of tRNAs, tiRNA, and tRFs can lead to tumor development and progression. Further studies focusing on the specific pathways of tRNA regulation could help identify tRNA biomarkers and therapeutic targets, which might prevent and treat cancers.

tRFUniverse: A comprehensive resource for the interactive analyses of tRNA-derived ncRNAs in human cancer

“… 34 , 51 , 52 , 66 , 67 Moreover, several studies have linked the dysregulation of these small RNA molecules with the development and progression of several different types of human cancers, suggesting their potential clinical applications as novel diagnostic and prognostic biomarkers or as innovative molecular targets. 68 , 69 , 70 , 71 However, more studies will be required to fully understand the biological functions of the tRNA-derived ncRNAs, especially in complex diseases such as cancer. In this context, bioinformatics and the increasing number of available databases and software for data analysis are providing new ways to study the biological functions of these fascinating regulatory small ncRNAs.…”

Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach

“…It is used to make proteins, and transfer RNA (tRNA) plays an important role in the epigenetic regulation of gene expression in tumors. A number of cell processes are mediated by tRNAs, including cell proliferation, signaling pathways, and stress responses, suggesting that tRNAs may also play a role in tumorigenesis and cancer progression [129]. As tRNA methyltransferase 1 (METTL1) levels increase with increasing glioma grade, the expression levels of METTL1 may be used to predict the prognosis of gliomas [130].…”

Crosstalk between Methylation and ncRNAs in Breast Cancer: Therapeutic and Diagnostic Implications

“…These housekeeping ncRNAs are expressed constitutively and are crucial for maintaining general cell function. tRNAs carry epigenetic modifications which are necessary for tRNA folding, stability, and function [ 116 ]. Martinez et al presented a paradigm that BCDIN3D is a cytoplasmic histidine transfer RNA-specific 5′-methyl phosphate cap synthase which efficiently monomethylates the 5′-monophosphate of cytoplasmic histidine transfer RNA, thus protecting the cytoplasmic histidine transfer RNA transcript from degradation in vitro [ 117 ].…”