Emerging role of transfer RNA-derived small RNAs (tsRNAs) in hepatocellular carcinoma

Transfer RNA-derived small RNAs (tsRNAs) have emerged as critical regulators in cancer biology, influencing gene expression, protein synthesis, and cellular signaling. Their unique expression patterns and functional diversity highlight their potential for diagnostic, prognostic, and therapeutic potential, particularly in hepatocellular carcinoma (HCC), a major cause of cancer-related mortality worldwide.

This review provides the first integrative overview of tsRNAs in HCC, encompassing their biogenesis, classification, molecular functions, and involvement in tumor hallmarks, including proliferation, metastasis, apoptosis, metabolism, angiogenesis, and immune modulation. We also summarize current advances in detection methods and databases and highlight the translational potential of tsRNAs as diagnostic, prognostic, and therapeutic targets. This work emphasizes unexplored dimensions of tsRNA-mediated regulation, connecting mechanistic insights with clinical applications.

Although tsRNAs show great promise in HCC diagnosis, prognosis, and therapy, clinical translation remains hindered by gaps in mechanistic understanding, technical challenges in detection, and a lack of large-scale validation. Overcoming these limitations through standardized methodologies and multi-omics integration could unlock their full potential in precision cancer medicine.