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Vol. 185, No. 1-3, 2007
Issue release date: June 2007
Cells Tissues Organs 2007;185:157–161

Transforming Growth Factor-β and microRNA:mRNA Regulatory Networks in Epithelial Plasticity

Zavadil J. · Narasimhan M. · Blumenberg M. · Schneider R.J.
aDepartment of Pathology and NYU Cancer Institute, and Departments of bMicrobiology and cDermatology, New York University School of Medicine, New York, N.Y., USA

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Noncoding microRNAs act as posttranscriptional repressors of gene function and are often deregulated in cancers and other diseases. Here we review recent findings on microRNA roles in tumorigenesis and report a microRNA profiling screen in transforming growth factor-β1 (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human keratinocytes, a model of epithelial cell plasticity underlying epidermal injury and skin carcinogenesis. We describe a novel EMT-specific microRNA signature that includes induction of miR-21, a candidate oncogenic microRNA associated with carcinogenesis. By integrating the microRNA screen results with target prediction algorithms and gene expression profiling data, we outline a framework for TGF-β-directed microRNA:messenger RNA (mRNA) regulatory circuitry and discuss its biological relevance for tumor progression.

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