Circular DNAs Participate in Tumorigenesis and Its Mechanisms

Chromosome-derived circular DNAs have different characters from linear DNAs and RNAs, which exert distinctive functions, and participate in a widespread range of physiological and pathological processes. Although, the composition, structure and genome-wide frequency of circular DNAs have not yet been illuminated systemically, circular DNAs are identified to act as unanticipated major sources of somatic rearrangements, which is an important genomic feature in tumorigenesis and represents a multihit and ongoing mutagenic process. And, this process remarkably contributes to oncogenic remodeling and oncogenes amplification through chimeric circularization and reintegration of circular DNAs into the linear genome, which is closely associated with high cancer mortality and morbidity. It has been found that circular DNAs-stimulated oncogenes amplification and overexpression implicate in diverse cytopathological processes during cancer progression, including cell proliferation, apoptosis, autophagy, epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) stiffness and angiogenesis. Herein, we comprehensively introduced circular DNAs’ formation and characteristics, and emphatically elaborated circular DNAs-induced oncogenes amplification and overexpression and their functional mechanisms regulating cancer behaviors. Lastly, some mysteries in oncogenic circular DNAs’ study were introduced, and the perspectives were also discussed in cancer diagnosis and treatment.