Identification and Characterization of Circular RNAs As a New Class of Putative Biomarkers in Human Blood

Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples.

共价闭合环状RNA分子（circRNAs）作为一类RNA异构体，近年已在动物界被发现具有广泛分布且组织特异性的表达特征，其表达通常独立于对应的线性mRNA。circRNAs是一类稳定性极强且有时可实现高表达的RNA分子。本研究对人体外周全血中的RNA进行测序，以探究circRNAs作为这种易于获取的体液中的生物标志物的潜力。本研究成功实现了数千种circRNAs的可重复性检测。尤为关键的是，本研究发现数百种circRNAs的表达量远高于对应的线性mRNA。因此，人体血液中的circRNA表达谱可揭示并量化数百个无法通过经典mRNA特异性检测方法分析的编码基因的活性。本研究结果表明，circRNAs可作为标准临床血液样本中的生物标志物分子。