Mohammad Salehi - Department of Medical Genetics, School of Advanced Technologiesin Medicine, Golestan University of Medical Sciences, Gorgan,Iran
Mohammad Javad Kamali - Department of Medical Genetics, School of Medicine, Babol Universityof Medical Sciences, Babol, Iran
Mohammad Shafiee - Department of Medical Genetics, School of Advanced Technologiesin Medicine, Golestan University of Medical Sciences, Gorgan,Iran
Ali Akbar Saffar Moghadam - Department of Medical Genetics, School of Advanced Technologiesin Medicine, Golestan University of Medical Sciences, Gorgan,Iran

Introduction: Non-coding RNAs (ncRNAs) play an integralrole in regulating a variety of biological processes and pathologicalconditions, including breast cancer. It is well known thatncRNAs play a crucial role in regulating intracellular signalingwhich controls cellular processes, including proliferation,apoptosis, invasion, migration, drug resistance, and activity ofestrogen receptor α. Recently, tRNA-derived fragments (tRFs)have gained increasing attention as one of the most intriguingclasses of ncRNAs. Evidence suggests that tRFs affect tumorinitiation and progression through the regulation of gene expressionat post-transcriptional levels, translational regulation,and epigenetic regulation.Materials and Methods: We provide a comprehensive reviewof the role of tRFs in breast cancer, including molecular mechanismsunderlying tRF-mediated regulation of tumor cell proliferation,apoptosis, metastasis, and drug resistance. This studyprovides an overview of papers that have been published onbreast cancer between ۲۰۱۰ to ۲۰۲۳ and are available on onlinedatabases including NCBI and Scopus.Results: In breast cancer pathogenesis, dysregulation of tRFshas been observed, suggesting that tRFs play an executive role.In our study, tRFs were found to have potential diagnostic andprognostic biomarkers, especially given their ability to enterbiofluids like serum, plasma, and saliva, and their changes reflectclinical findings in patients. So, they can be introducedas novel non-invasive biofluid-based tumor markers with highsensitivity and specificity. Notably, a set of tRFs may serve asnovel potential therapeutic targets for developing new targetedtherapy approaches in clinical settings.Conclusion: The study highlights the latest insights into the contributions of tRFs in the normal function of breast cells andalso their dysregulation in proliferation, apoptosis, shaping ofthe metastasis environment, and drug resistance. The recentfindings can provide a basis for future studies on tRFs whichhave proven to have the potential to act as game-changing therapeutictargets for tackling cancer, and the design and developmentof novel diagnostic and prognostic approaches.

tRNA-derived fragment, Breast cancer, Diagnosis,Biomarker, Targeted Therapy