Circular RNAs and cancer: Opportunities and challenges.

Circular RNAs (circRNAs) are covalently circularized RNA moieties that despite being relatively abundant were only recently identified and have only begun to be investigated within the last couple of years. Even though there are many thousands of genes that appear capable of producing circRNAs, and the fact that many circRNAs appear to be highly evolutionarily conserved, the function of all but a few remain to be fully explored. What has been determined, however, is that circRNAs play key regulatory roles in many aspects of biology with focus being given to their function in cancer. Most of the studies to date have found that circRNAs act as master regulator of gene expression most often than not acting to regulate levels though sequestration or "sponging" of other gene expression regulators, particularly miRNAs. They can also function directly modulating transcription, or by interfering with splicing mechanisms. Some circRNAs can also be translated into functional proteins or peptides. A combination of tissue and developmental stage specific expression along with an innate resistance to RNAse activity means that circRNAs show perhaps their greatest potential as novel biomarkers of cancer. In this chapter we consider the current state of knowledge regarding these molecules, their synthesis, function, and association with cancer. We also consider some of the challenges that remain to be overcome to allow this emerging class of RNAs to fulfill their potential in clinical practice.