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

Zavadil J.a · Narasimhan M.b · Blumenberg M.c · Schneider R.J.b
aDepartment of Pathology and NYU Cancer Institute, and Departments of bMicrobiology and cDermatology, New York University School of Medicine, New York, N.Y., USA Cells Tissues Organs 2007;185:157–161 (DOI:10.1159/000101316)

Abstract

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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