tRNA‐derived fragments: Unveiling new roles and molecular mechanisms in cancer progression

Abstract tRNA‐derived fragments (tRFs) are novel small noncoding RNAs (sncRNAs) that range from approximately 14 to 50 nt. They are generated by the cleavage of mature tRNAs or precursor tRNAs (pre‐tRNAs) at specific sites. Based on their origin and length, tRFs can be classified into three categories: (1) tRF‐1 s; (2) tRF‐3 s, tRF‐5 s, and internal tRFs (i‐tRFs); and (3) tRNA halves. They play important roles in stress response, signal transduction, and gene expression processes. Recent studies have identified differential expression of tRFs in various tumors. Aberrantly expressed tRFs have critical clinical value and show promise as new biomarkers for tumor diagnosis and prognosis and as therapeutic targets. tRFs regulate the malignant progression of tumors via various mechanisms, primarily including modulation of noncoding RNA biogenesis, global chromatin organization, gene expression regulation, modulation of protein translation, regulation of epigenetic modification, and alternative splicing regulation. In conclusion, tRF‐mediated regulatory pathways could present new avenues for tumor treatment, and tRFs could serve as promising therapeutic targets for cancer therapy.