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Review
. 2025 Jul 11:15:65-73.
doi: 10.1016/j.ncrna.2025.07.003. eCollection 2025 Dec.

Emerging roles of tsRNAs in programmed cell death and disease therapeutics: challenges, opportunities, and future directions

Affiliations
Review

Emerging roles of tsRNAs in programmed cell death and disease therapeutics: challenges, opportunities, and future directions

Zhe Li et al. Noncoding RNA Res. .

Abstract

Programmed cell death (PCD), which includes various forms such as apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis, plays a pivotal role in disease pathogenesis and progression. tRNA-derived small RNAs (tsRNAs) have emerged as crucial regulators of these processes, influencing cellular fate and disease outcomes. Research has revealed diverse expression profiles of tsRNAs across various diseases, emphasizing their roles in modulating PCD pathways and their potential value in diagnosis and treatment. Specific tsRNAs can either promote or inhibit apoptosis; for example, tsRNA-3043a promotes ovarian granulosa cell apoptosis in premature ovarian insufficiency, whereas tsRNA-04002 prevents apoptosis in nucleus pulposus cells to delay intervertebral disc degeneration. Furthermore, tsRNAs serve as potential biomarkers for early disease detection, with emerging detection technologies enhancing their clinical utility. Therapeutically, tsRNA-targeted strategies, such as RNA interference and exosome-based drug delivery, offer new avenues for modulating PCD in diseases such as cancer, cardiovascular disorders, and neurodegenerative diseases. Despite challenges in understanding tsRNA biogenesis and functional diversity, their roles in regulating PCD highlight their strong potential in advancing disease diagnostics, treatment strategies, and personalized medicine.

Keywords: Clinical translation; Diagnostic biomarkers; Programmed cell death (PCD); Therapeutic targets; tsRNAs (tRNA-derived small RNAs).

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Schematic representation of tsRNA-mediated regulation in various forms of programmed cell death.
Fig. 2
Fig. 2
Clinical applications and future directions of tsRNAs in disease diagnosis, mechanism exploration, and therapeutic development.

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