tRNA‐derived fragments in gastric cancer: Biomarkers and functions

Abstract

tRNA‐derived fragments (tRFs), non‐coding RNAs that regulate protein expression after transcription, have recently been identified as potential biomarkers. We identified differentially expressed tRFs in gastric cancer (GC) and the biological properties of tRFs in predicting the malignancy status of GCs as possible biomarkers. Until 15 February 2022, two independent reviewers did a thorough search in electronic databases of Scopus, EMBASE and PubMed. The QUADAS scale was used for quality assessment of the included studies. Ten articles investigating the clinical significance of tRFs, including 928 patients, were analysed. In 10 GC studies, seven tRFs were considerably upregulated and five tRFs were significantly downregulated when compared to controls. Risk of bias was rated low for index test, and flow as well as timing domains in relation to the review question. The applicability of the index test, flow and timing and patient selection for 10 studies was deemed low. In this study, we review the advances in the study of tRFs in GC and describe their functions in gene expression regulation, such as suppression of translation, cell differentiation, proliferation and the related signal transduction pathways associated with them. Our findings may offer researchers new ideas for cancer treatment as well as potential biomarkers for further research in GC.

Application of serum gastric function markers and digestive tumor indices to the diagnosis of early gastric cancer and precancerous lesions

“…16 Another study revealed the advances of tRFs in GC and their functions in gene expression regulation and the related signal transduction pathways associated with them. 17 On the basis of the previous and present study, we believe that PGI and G-17 are valuable for differentiating EGC and gastric IN. However, the small number of samples and operator error might have influence on the accuracy of the result.…”

Dysregulation of tRNA methylation in cancer: Mechanisms and targeting therapeutic strategies

“…When tRNA is not sufficiently modified, tRNA stability could be disrupted and cleaved to tRFs or degraded by Dicer, endonuclease Z (RNase Z/ELAC2) and other RNA endonucleases (RNases) [ 15 – 17 ]. tRFs/tiRNAs are categorized into five types based on their cleavage sites on mature tRNA by different nucleases, including 5’-half, 3’-half, 5’-tRF, 3’-tRF, and i-tRF [ 18 – 20 ]. Among them, 5’-half and 3’-half are usually produced under various stress conditions in cells, generated by the activation of angiogenin (ANG) enzyme activity, which cleaves tRNA at the anticodon site [ 21 , 22 ].…”

Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer

“…The authors developed a GC diagnostic model containing three tRFs (tRF-52:76-Val-AAC-1-M3, tRF-59:76-Val-AAC-1-M5, and tsRNA-39:74-tRNA-Val-AAC-1-M3) with a mean AUC of 0.815, demonstrating greater sensitivity and specificity for GC diagnosis than the commonly used clinical markers and each of the three tRF biomarkers. The results suggested that plasma exosome tRF-52:76-Val-AAC-1-M3, tRF-59:76-Val-AAC-1-M5, and tsRNA-39:74-tRNA-Val-AAC-1-M3 are biomarkers for GC diagnosis and prognosis and help to identify and diagnose GC patients with a high risk of recurrence and poor prognosis ( 31 , 62 ).…”