Comprehensive profiling of tsRNAs in acute coronary syndrome: expression patterns, clinical correlations, and functional insights

Transfer RNA-derived small RNAs (tsRNAs) have emerged as potential biomarkers of various human diseases. However, the clinical utility and biological functions of tsRNA in acute coronary syndrome (ACS) remain poorly understood. To investigate this, we performed high-throughput small RNA sequencing on peripheral blood monocyte cells (PBMCs) from 24 ACS patients and 12 healthy controls. Our analysis revealed distinct and characteristic expression patterns of tsRNAs in response to ACS, highlighting their potential as disease signatures in human PBMCs. Differentially expressed tsRNAs were validated using RT-qPCR in two independent case-control sets. Among these, tRF-Gly-GCC-06 was significantly upregulated in volunteers with unstable angina (UA) and acute myocardial infarction (AMI) (p < 0.05) and showed a statistically significant positive correlation with the Gensini score (r = 0.353, p < 0.001). Moreover, this tsRNA was independently associated with an increased risk of ACS after adjusting for conventional cardiovascular risk factors (odds ratio (OR) = 1.58, 95% confidence interval (CI): 1.37-1.83, p < 0.001). A series of functional studies showed that tRF-Gly-GCC-06 significantly facilitated macrophage proliferation and migration and modulated inflammation-related gene expression in vitro. This study identified a novel functional gene associated with ACS, tRF-Gly-GCC-06, as a potential clinical biomarker and therapeutic target.