The control of tumor progression by circular RNAs: novel prognostic and therapeutic insights resulting from the analysis of the circAGO2/human antigen R complex

Circular RNAs (circRNAs) represent a relatively novel class of non-coding RNA (ncRNA) characterized by a covalently bound loop (1). Due to their circular structure, circRNAs are very stable and resistant to the action of exonucleases and this characteristic distinguishes them from the other linear RNAs (2). They belong to the largest class of long ncRNA (lncRNA), and consist of several hundred nucleotides; they are endogenous, abundantly expressed, conserved and able to perform own peculiar functions (3,4). Depending on where they are located on the genome, members of this class are distinguished in exonic, intronic, and eso-intronic (3). As far as their biogenesis is concerned, it has now been found that they are co-transcriptional products, being generated through back-splicing, unlike messenger RNA of genes coding for proteins (5). Interestingly, they are able to regulate gene expression both at transcriptional and post-transcriptional levels, essentially through three main mechanisms: (I) they can function as endogenous sponge for microRNAs (miRNAs), (II) they can bind to RNA-binding proteins (RBP) and, finally, (III) they can interact with other RNAs through base-pairing (3)