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

Ece Gumusoglu-Acar; Cansu Dilara Ok; Zhazira Zhonderbek; Tuba Gunel

doi:10.5606/fng.btd.2026.218

Ece Gumusoglu-Acar¹, Cansu Dilara Ok², Zhazira Zhonderbek², Tuba Gunel¹

¹Department of Molecular Biology and Genetics, İstanbul University, Faculty of Science, İstanbul, Türkiye
²Department of Molecular Biotechnology and Genetics, İstanbul University, Institute of Science, İstanbul, Türkiye

Keywords: Cancer biomarkers, tiRNAs, tRFs, tRNA modifications. tRNA-derived fragments.

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.