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tRNA modifications in cancer: from molecular mechanisms to clinical translation

Cillian H Cheng1, Chi Chun Wong2

  • 1Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. chenghc95@gmail.com.

Biomarker Research
|April 11, 2026
PubMed

Insights

Transfer RNA (tRNA) modifications are crucial in cancer, acting as biomarkers and therapeutic targets. Understanding their role in protein expression and cell phenotypes is key for clinical applications.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Transfer RNA (tRNA) modifications are diverse RNA modifications with critical cellular functions.
  • Defects in tRNA modifications and tRNA fragmentation are observed across various cancer types.
  • tRNA modification enzymes can act as oncogenes or tumor suppressors.

Purpose of the Study:

  • To summarize the current understanding of tRNA modifications in cancer.
  • To outline the translational and clinical implications of tRNA modifications for cancer diagnosis and treatment.
  • To discuss the influence of tRNA modifications on protein expression, molecular mechanisms, and cell phenotypes.

Main Methods:

  • Literature review and synthesis of existing research on tRNA modifications in cancer.
  • Analysis of mechanistic studies on tRNA modification enzymes in cancer initiation, progression, and therapy resistance.
  • Discussion of clinical implications and translational challenges.

Main Results:

  • tRNA modifications play vital roles in cancer initiation, progression, metastasis, metabolic rewiring, therapy resistance, and immune evasion.
  • tRNA modification enzymes have significant potential as oncogenes or tumor suppressors.
  • tRNA modifications influence target tRNA fate, protein expression, and cell phenotypes.

Conclusions:

  • tRNA modifications represent promising diagnostic and prognostic biomarkers in cancer.
  • Targeting tRNA modification machinery offers therapeutic potential for cancer treatment.
  • Overcoming hurdles in translating tRNA modification research into clinical practice is essential.
Keywords:
CancerClinical applicationsMolecular mechanismsTransfer RNA (tRNA)tRNA modificationtRNA-derived RNAs (tdRs)

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