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Abstract
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The epithelial-mesenchymal transition (EMT), characterized by the loss of cell-cell adhesion in epithelial cells and the acquisition of motile and invasive properties in mesenchymal cells, is one key mechanism by which tumors of epithelial origin acquire the capability to undergo tissue invasion and metastasis. An underlying principle of EMT is that global changes in the gene regulatory network drive transformation in cell phenotype during this process. While recent studies have characterized the transcriptional network of EMT, the roles of post-transcriptional processes such as alternative splicing and polyadenylation are poorly understood. In this talk, I will introduce computational and statistical methods we developed for global analysis of post-transcriptional gene regulation using high-throughput sequencing technologies. Through the use of integrated genomic, computational, and molecular approaches, we have elucidated the genome-wide landscape of alternative splicing during EMT. This cell-type-specific splicing network is globally switched in in vitro and in vivo models of cancer invasion and metastasis, and represents a robust molecular signature of cancer cells with invasive properties and aggressive phenotypes. Our study provides a comprehensive picture of an extensive EMT-regulated post-transcriptional RNA network in development and cancer.
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