CircRNAs and Fusion-circRNAs in cancer: New players in an old game.

Circular RNAs (circRNAs) are generated from 'back-splicing' events. Their circular structure makes them stable in cells and body fluids. These entities are involved in several human diseases including cancer, as they affect the expression of genes promoting proliferation, invasion, apoptosis, and angiogenesis. Moreover, they are secreted in extracellular vesicles, such as exosomes, having a potential role as messengers in cell-to-cell communications. CircRNAs are also generated by the back-splicing of linear fusion transcripts derived from genomic rearrangements, giving rise to fusion circRNAs (f-circRNAs). Here we discuss the most relevant results achieved by studying the role of circRNAs in cancer onset and progression, particularly focusing on f-circRNAs in hematological and solid tumors. Moreover, we report recent advances in the application of circRNAs as novel "liquid biopsy" biomarkers for early and non-invasive diagnosis of tumors, and as therapeutic targets in human cancer. Their use as engineered molecules sponging oncogenic miRNAs or stably expressing proteins/drugs is also discussed. All these achievements suggest the crucial importance of circRNAs and f-circRNAs in the future setup of personalized therapies in molecular medicine.