Circles reshaping the RNA world: from waste to treasure

Jing Liu, Tian Liu, Xiaman Wang, Aili He

A new type of RNAs was identified from genes traditionally thought to express messenger or linear ncRNA (noncoding RNA) only. They were subsequently named as circRNAs (circular RNAs) due to the covalently closed structure. Accumulating studies were performed to explore the expression profile of circRNAs in different cell types and diseases, the outcomes totally changed our view of ncRNAs, which was thought to be junk by-products in the process of gene transcription, and enriched our poor understanding of its underlying functions. The expression profile of circRNAs is tissue-specific and alters across various stages of cell differentiation. The biological function of circRNAs is multi-faceted, involving five main features (sponge effect, post-transcriptional regulation, rolling circle translation, circRNA-derived pseudogenes and splicing interference) and varying differently from the locations, binding sites and acting modes of circRNAs. The regulating role of circRNAs is not isolated but through an enormous complicated network involving mRNAs, miRNAs and proteins. Although most of the potential functions still remain unclear, circRNAs have been proved to be ubiquitous and critical in regulating cellular processes and diseases, especially in cancers, from the laboratory to the clinic. Herein, we review circRNAs' classification, biogenesis and metabolism, their well-studied and anticipated functions, the current understanding of the potential implications of circRNAs in tumorigenesis and cancer targeted therapy.