Executive Summary : | MicroRNAs, including tRF (tRNA derived fragments) and tsRNAs (tRNA halves), are emerging biomarkers for diagnostic, prognostic, and treatment response. These non-coding small RNAs are both nuclear and mitochondrial in origin and are classified into three subclasses: tRF-5, tRF-3, and tRF-1. They have been found to modify gene expression and contribute to development, differentiation, inflammation, and oncogenesis. Analyzing naked miRNAs as a biomarker in clinical settings is challenging due to the lack of standardization in blood samples. Exosomal content is stable and cell-specific, making it reasonable to analyze exosomal ncRNAs for clinical samples. Interestingly, tRFs are found in exosomes, suggesting that miRNAs are generated from tRNAs. To catalogue overlapping sequences between tRNA derived miRNAs and tRFs, in silico analysis was conducted. Results suggest that miR-3182, miR-4521, miR-1260a, miR-1260b, and miR-7977 are found within human nuclear tRFs. Breast cancer biomarkers miR-16-5p and miR-93-5p shared common targets with tRF-harvested miRNAs miR-1260a and miR-4521. Survival analysis plotted using clinical data showed that high expression of miR-4521, miR-1260a, and miR-93 correlated with low survival. Generating miRNAs from tRNA may be more feasible for cancer cells than following the canonical pathway, and future studies should explore mechanisms in the context of cancer therapeutics. The proposal aims to explore the generation of miRNAs/tRFs from tRNAs, as these miRNAs are involved in breast carcinogenesis. |