Recent evidence suggests that RNAs compete for binding and regulation by a finite pool of microRNAs (miRs), thus regulating each other through a competing endogenous RNA (ceRNA) mechanism. I propose to systematically study ceRNA interactions in cancer by reverse-engineering context-specific miR-RNA interactions and ceRNA regulatory interactions across multiple tumor types and study the effecs of these interactions in cancer. I will attempt to use ceRNA interactions to explain how genetic and epigenetic alterations are propagated to target established drivers of tumorigenesis. Using bioinformatics analysis of primary tumor samples and experimental validation in cell lines, I will investigate the roles that mRNAs and noncoding RNAs can play in tumorigenesis via ceRNA interactions. Specifically, I will study how RNAs target tumor-suppressors and oncogenes as ceRNAs, and attempt to accounting for some of the missing genomic variability in tumors.