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The tRNA landscape in cancer: from pathogenesis to therapeutic interventions

Ni Jian1,2, Han Ren2,3, Yingqi Huang1,2

  • 1School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China.

Acta Biochimica Et Biophysica Sinica
|June 17, 2026
PubMed

Insights

Transfer RNA (tRNA) is crucial for protein synthesis and cancer development. Disruptions in tRNA regulation, including expression, modifications, and tRNA-derived small RNAs (tdRs), promote tumor growth and resistance.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Transfer RNA (tRNA) is essential for protein synthesis.
  • Dysregulated tRNA mechanisms are increasingly recognized in cancer development.
  • The tumor microenvironment influences tRNA reprogramming.

Purpose of the Study:

  • To systematically review aberrant tRNA-related mechanisms in cancer.
  • To highlight the role of tRNA in tumor progression and therapeutic resistance.
  • To explore novel therapeutic strategies targeting tRNA pathways.

Main Methods:

  • Systematic review of literature on tRNA in cancer.
  • Analysis of tRNA expression profiles, modifications, aminoacylation, tdRs, trafficking, and fidelity.
  • Examination of the interplay between the tumor microenvironment and tRNA.

Main Results:

  • Altered tRNA expression, modifications, aminoacylation, tdRs, trafficking, and fidelity are common in cancer.
  • Tumor microenvironment shapes tRNA reprogramming for adaptive survival.
  • Dysregulated tRNA elements drive cancer stem cell properties and therapeutic resistance.
  • tRNA alterations reprogram the oncoproteome and signaling networks, promoting proliferation, metastasis, immune evasion, and drug resistance.

Conclusions:

  • Targeting tRNA mechanisms offers promising novel cancer therapies.
  • Strategies include using suppressor tRNAs, tdRs, or inhibiting tRNA biogenesis enzymes.
  • Remodeling the dysfunctional tRNA network in cancer provides new therapeutic avenues.
Keywords:
aminoacyl-tRNA synthetasescancermisreading tRNAssup-tRNAstRNAtRNA modificationstdRs

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