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Review
. 2025 Mar 12;44(1):38.
doi: 10.1007/s10555-025-10254-6.

The functions and modifications of tRNA-derived small RNAs in cancer biology

Abdulaziz Ahmed A Saad #  1 , Kun Zhang #  2 , Qianqian Deng  1 , Jiawang Zhou  1 , Lichen Ge  3 , Hongsheng Wang  4
Affiliations
Review

The functions and modifications of tRNA-derived small RNAs in cancer biology

Abdulaziz Ahmed A Saad et al. Cancer Metastasis Rev. .

Abstract

Recent progress in noncoding RNA research has highlighted transfer RNA-derived small RNAs (tsRNAs) as key regulators of gene expression, linking them to numerous cellular functions. tsRNAs, which are produced by ribonucleases such as angiogenin and Dicer, are classified based on their size and cleavage positions. They play diverse regulatory roles at the transcriptional, post-transcriptional, and translational levels. Furthermore, tRNAs undergo various modifications that influence their biogenesis, stability, functionality, biochemical characteristics, and protein-binding affinity. tsRNAs, with their aberrant expression patterns and modifications, act as both oncogenes and tumor suppressors. This review explores the biogenetic pathways of tsRNAs and their complex roles in gene regulation. We then focus on the importance of RNA modifications in tsRNAs, evaluating their impact on the biogenesis and biological functions on tsRNAs. Furthermore, we summarize recent data indicating that tsRNAs exhibit varied expression profiles across different cancer types, highlighting their potential as innovative biomarkers and therapeutic targets. This discussion integrates both existing and new knowledge about tsRNAs, emphasizing their importance in cancer biology and clinical advancement.

Keywords: Biomarker; Cancer; RNA modifications; Therapy target; tRNA-derived fragments.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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