Simone Avesani, Luciano Cascione, Rosalba Giugno
Circular RNAs (circRNAs) represent an emerging class of noncoding RNAs characterized by their covalently closed-loop structure and generated through the back-splicing event. This structural configuration provides circRNAs with enhanced stability and unique functional properties. Functionally, circRNAs act as protein scaffolds, enhance protein activity, can be translated, and frequently serve as competing endogenous RNAs (ceRNAs), particularly by sponging microRNAs (miRNAs) and modulating downstream gene expression. Since these regulatory capacities have significant implications in cancer, neurodegenerative, and cardiovascular diseases, in response, numerous computational approaches have been developed to reconstruct circRNA-miRNA-mRNA networks, ranging from specific circRNA-oriented applications to sequencing-based tools, each with distinct strengths and limitations. This chapter provides an overview of these strategies, highlighting their application in bioinformatics research and their potential to explore novel regulatory mechanisms mediated by circRNAs.