• The potential of tRFs as therapeutic targets and diagnostic biomarkers in breast cancer
  • Nooshafarin Shirani,1,*
    1. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.


  • Introduction: Recent advances in molecular biology, such as high-throughput RNA sequencing, have revealed the potential of small non-coding RNAs (sncRNAs) as key players in the regulation of gene expression and cancer development. Transfer RNA (tRNA)-derived fragments (tRFs) are small RNA molecules of approximately 20 nucleotides in length that are produced through the cleavage of pre-tRNA and mature tRNA. Although tRFs were initially disregarded as incidental products of tRNA turnover, there is accumulating evidence that supports the functionality of tRFs and their association with various human diseases, including cancer. Moreover, they are conserved sequences that are widely distributed in different species and in various human body fluids. This review article examines the current understanding of the role of tRFs in the molecular mechanisms of breast cancer, focusing on their potential as therapeutic targets and diagnostic biomarkers.
  • Methods: A comprehensive literature search was conducted, focusing on recent studies, including in silico, in vitro, and in vivo research. Data were collected from databases such as PubMed, Scopus, Google Scholar, and Web of Science using search terms like breast cancer, tRFs, biomarkers, molecular mechanisms, diagnosis, and treatment. After a thorough search, the essential information about tRFs, their biological function, and their diagnostic and therapeutic value in breast cancer was identified.
  • Results: The analysis revealed that dysregulations of tRFs are highly associated with breast cancers, including the regulation of tumor cell proliferation, invasion, migration, and drug resistance. They exert their role through various processes such as modulation of mRNA stability, the translation process, cellular stress, immune response, and differentiation. For example, one study found that three tRFs (tRF-Gly-CCC-046, tRF-Tyr-GTA-010, and tRF-Pro-TGG-001) were downregulated in both breast cancer and early breast cancer compared to healthy donors. This suggests that these tRFs could potentially serve as novel circulating biomarkers for the early detection of breast cancer. In addition, tRF-17-79MP9PP has been shown to play an important role in inhibiting the malignant activities of cells and to function as a novel tumor suppressor in breast cancer via the THBS1/TGF-β1/Smad3 pathway.
  • Conclusion: Early detection, diagnosis, and treatment of breast cancer are crucial for a successful cure. While conventional methods like breast imaging and needle core biopsy have their limitations, new non-invasive strategies such as tRFs could be effective in the treatment of breast cancer. The unique expression patterns of tRFs suggest not only their potential as biomarkers for early diagnosis but also possible therapeutic interventions. However, further research should focus on understanding the specific mechanisms by which tRFs influence the development of breast cancer and investigating their utility in the clinical setting.
  • Keywords: breast cancer, tRNA-derived fragment, biomarkers, treatment , diagnosis