Transforming growth factor-beta and microRNA:mRNA regulatory networks in epithelial plasticity.
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-beta1 (TGF-beta)-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-beta-directed microRNA:messenger RNA (mRNA) regulatory circuitry and discuss its biological relevance for tumor progression.
Zavadil
Jiri
J
Department of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. jiri.zavadil@med.nyu.edu
Narasimhan
Manisha
M
Blumenberg
Miroslav
M
Schneider
Robert J
RJ
D000465:Algorithms; D000818:Animals; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D035683:MicroRNAs; D016212:Transforming Growth Factor beta