Establishing essential quality criteria for the validation of circular RNAs as biomarkers

Non-coding RNAs were established in the last decade as a new valuable biomarker class for human diseases. Specifically, circular RNAs (circRNAs) were only recently discovered as a new large group of non-coding RNAs that, due to their circular configuration, are metabolically more stable compared to their linear counterparts and therefore highly suitable for biomarker use. Based on high-throughput sequencing, the catalogs of endogenous circRNAs with disease relevance and correlation continue to grow steadily. As a consequence, circRNAs emerged as novel and attractive biomarkers, indicated by numerous recent publications. Here we would like to stress the need of essential quality criteria for validation and characterization of circular RNAs. In addition to high-throughput sequencing, classical biochemical methods are essential and should be applied for the characterization of this special class of RNAs, in particular to convincingly confirm their circularity.