He Yi, Wang Jing, Chen Chen, Wang Rongli, Ma Xiaozhu, Ma Ruiying, Sun Yang, Wang Luyun, Ding Hu
Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, P.R. China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, P.R. China.
Hum Genet. 2025 May;144(5):575-590. doi: 10.1007/s00439-025-02742-0. Epub 2025 Apr 15.
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.
转运RNA衍生的小RNA(tsRNAs)已成为多种人类疾病的潜在生物标志物。然而,tsRNA在急性冠状动脉综合征(ACS)中的临床应用和生物学功能仍知之甚少。为了对此进行研究,我们对24例ACS患者和12名健康对照者的外周血单核细胞(PBMCs)进行了高通量小RNA测序。我们的分析揭示了tsRNAs在应对ACS时独特且具有特征性的表达模式,突显了它们作为人类PBMCs中疾病特征的潜力。在两个独立的病例对照组中,使用RT-qPCR对差异表达的tsRNAs进行了验证。其中,tRF-Gly-GCC-06在不稳定型心绞痛(UA)和急性心肌梗死(AMI)志愿者中显著上调(p < 0.05),并且与Gensini评分呈统计学显著正相关(r = 0.353,p < 0.001)。此外,在调整传统心血管危险因素后,这种tsRNA与ACS风险增加独立相关(优势比(OR) = 1.58,95%置信区间(CI):1.37 - 1.83,p < 0.001)。一系列功能研究表明,tRF-Gly-GCC-06在体外显著促进巨噬细胞增殖和迁移,并调节炎症相关基因表达。本研究鉴定出一个与ACS相关的新功能基因tRF-Gly-GCC-06,作为潜在的临床生物标志物和治疗靶点。