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p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2.

By T. Kim, A. Veronese, F. Pichiorri, T. J. Lee, Y. Jeon, S. Volinia, P. Pineau, A. Marchio, J. Palatini, S. Suh, H. Alder, C. Liu, A. Dejean and C. M. Croce

Abstract

p53 suppresses tumor progression and metastasis. Epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT

Topics: Carcinoma, Hepatocellular, genetics/metabolism/pathology, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Homeodomain Proteins, biosynthesis/genetics, Humans, Liver Neoplasms, genetics/metabolism/pathology, Male, MicroRNAs, genetics/metabolism, Neoplasm Metastasis, RNA, Neoplasm, genetics/metabolism, Repressor Proteins, biosynthesis/genetics, Transcription Factors, biosynthesis/genetics, Transcriptional Activation, genetics, Tumor Suppressor Protein p53, genetics/metabolism
Year: 2011
DOI identifier: 10.1084/jem.20110235
OAI identifier: oai:iris.unife.it:11392/1682305
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