Analysis of the role of miRNAs in ovarian cancer metastasis
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Cancer mortality is primarily due to metastasis. Metastasis is a complex multi-step process involving, on the molecular level, regulatory control of two key development pathways: epithelial-to-mesenchymal transition (EMT) and it reciprocal, mesenchymal-to-epithelial transition (MET) . MiRNAs are small regulatory RNA molecules that play key roles in the regulation of EMT/MET. In this thesis, I examine the role of miRNAs in regulating EMT/MET in ovarian cancer. In the first study, I show that sequentially divergent miRNAs converge to regulate the EMT/MET process through both direct and indirect regulatory changes. In the second study, I explore the impact of genetic difference between different cancer cell lines on the function of miRNAs to regulate the EMT/MET process. In the third study, I evaluate the importance of post-transcriptional/translational changes in the metastasis of a stage III ovarian cancer patient and the role played by miRNAs in regulating the process.