An Overview of the Computational Models Dealing with the Regulatory CeRNA Mechanism and CeRNA Deregulation in Cancer

Pools of RNA molecules can act as competing endogenous RNAs (ceRNAs) and indirectly alter their expression levels by competitively binding shared microRNAs. This ceRNA cross talk yields an additional posttranscriptional regulatory layer, which plays key roles in both physiological and pathological processes. MicroRNAs can act as decoys by binding multiple RNAs, as well as RNAs can act as ceRNAs by competing for binding multiple microRNAs, leading to many cross talk interactions that could favor significant large-scale effects in spite of the weakness of single interactions. Identifying and studying these extended ceRNA interaction networks could provide a global view of the fine-tuning gene regulation in a wide range of biological processes and tumor progressions. In this chapter, we review current progress of predicting ceRNA cross talk, by summarizing the most up-to-date databases, which collect computationally predicted and/or experimentally validated miRNA-target and ceRNA-ceRNA interactions, as well as the widespread computational methods for discovering and modeling possible evidences of ceRNA-ceRNA interaction networks. These methods can be grouped in two categories: statistics-based methods exploit multivariate analysis to build ceRNA networks, by considering the miRNA expression levels when evaluating miRNA sponging relationships; mathematical methods build deterministic or stochastic models to analyze and predict the behavior of ceRNA cross talk.