Aberrantly Expressed CeRNAs Account for Missing Genomic Variability of Cancer Genes via MicroRNA-Mediated Interactions

There is growing evidence 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. My dissertation work focused on systematically studying ceRNA interactions in cancer by reverse-engineering context-specific miR-RNA interactions and ceRNA regulatory interactions across multiple tumor types and study the effects of these interactions in cancer. I attempted 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 have investigated the roles that mRNAs and noncoding RNAs can play in tumorigenesis via ceRNA interactions. Specifically, I studied how RNAs target tumor-suppressors and oncogenes as ceRNAs, and attempted to accounting for some of the missing genomic variability in tumors.