The roles of tRNA-derived fragments and tRNA modifications in cancer: Diagnostic and therapeutic perspectives

Abstract

Transfer ribonucleic acid (tRNA)-derived small RNAs (tsRNAs), including tRNA-derived fragments (tRFs) and tRNA halves, are factors that significantly contribute to the initiation, progression, and resistance to treatment processes of cancer. It is shown that tRNA processing, cleavage, and modification patterns are significantly altered in many types of malignancies. These alterations influence codon-dependent translation, messenger RNA stability, cellular stress responses, and the accuracy of protein synthesis, thereby promoting tumor growth and metastatic potential. Irregular tRNA modifications can reprogram translation to support oncogenic signaling and create therapeutic vulnerabilities. Therefore, targeting tRNA-modifying enzymes and reprogramming translation has been proposed as a promising therapeutic strategy. The presence and stability of tsRNAs in diverse biofluids, including plasma, serum, urine, and cerebrospinal fluid, underscore their potential as non-invasive diagnostic biomarkers. Studies show that circulating tsRNAs correlate with tumor stage, metastasis, recurrence risk, and overall survival, and may provide higher diagnostic accuracy than traditional microRNAs. This study highlights the role of tRNA modifications and tRFs in cancer biology, translational regulation, and precision diagnostics.

Cite this article as: Gumusoglu-Acar E, Ok CD, Zhonderbek Zh, Gunel T. The roles of tRNAderived fragments and tRNA modifications in cancer: Diagnostic and therapeutic perspectives. D J Med Sci 2026;12(1):48-60. doi: 10.5606/fng. btd.2026.218.

E.G.A.: Contributed to the conception and design of the study, supervision of the research process, analysis and interpretation of the data, manuscript writing, critical revision of the article, and references and funding management; T.G.: Contributed to the design and supervision of the study, manuscript writing, and references and funding management; C.D.O.: Contributed to data collection and processing, analysis and interpretation of the data, literature review, manuscript writing, and provision of materials; Z.Z.: Contributed to data collection and processing, analysis and interpretation of the data, literature review, manuscript writing, and provision of materials.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Data Sharing Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.

The authors received no financial support for the research and/or authorship of this article.

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Artificial intelligence (AI) tools were used for figure generation through an AI-assisted coding approach implemented in Google Colab. All generated outputs were critically reviewed, validated, and approved by the authors. AI tools were not used for data analysis, interpretation, or the formulation of conclusions. All scientific content and conclusions are the sole responsibility of the authors. The authors confirm that no AI tools were used to generate or fabricate references and that all references have been verified for accuracy.