circRNAs and miRNAs in the diagnosis of hepatocellular carcinoma: the long race to new targets

The work by Yu and colleagues, recently published on the Journal of Hepatology (1) represents the latest step on a greatly debated and cherished argument: the mechanisms and clinical applicability of circular RNAs (circRNAs) and other non-coding RNAs (in primis microRNAs) in human tumoral disease, and in hepatocellular carcinoma (HCC) in particular. From their discovery in plants in 1976 no particular attention was attributed to the role of circRNAs in human, as they were considered as viroids (2). However, since 2012 we are experiencing a fast-growing interest towards circRNA functions in human: respectively 3 articles were published in 2013, 37 in 2015, 241 in 2017 and already 168 articles are available in May 2018 (source: https://www.ncbi.nlm.nih.gov/pubmed). circRNAs are very stable RNA structures, closed by a continuous loop, present in cell cytoplasm (3). They are highly represented in eukaryotic cells: up to now thousands of circRNAs have been identified in human. Among the circRNA functions, to “sponge” miRNAs is the most important: in this way circRNAs regulate miRNA concentration and—as a consequence—regulate the expression of several genes at transcriptional or post-transcriptional level (4).