Stabilization of Snail by HuR in the process of hydrogen peroxide induced cell migration

Snail functions as a key regulator in the induction of a phenotypic change called epithelial to mesenchymal transition (EMT). Aberrant expression of Snail prevails in the onset and development of tumor. Here, we have observed increased expression of Snail under the treatment of hydrogen peroxide (H2O2). Investigation into the underlying mechanisms revealed that stabilization of Snail mRNA contributes partially to this process. H2O2-induced the lucifierase activity of the reporter construct contains the 3'UTR of Snail. Deletion of the AU-rich elements in the UTR eliminated the response of the reporter to H2O2, Suggesting the potential role of HuR in the process. Lowering of endogenous HuR levels through knockdown of HuR by siRNA greatly reduced the inducability and half-life of Snail mRNA, which consequently inhibited the downregulation of E-cadherin by H2O2. Our findings indicate that HuR plays a major role in regulating H2O2-induced Snail expression by enhancing Snail mRNA stability, which in turn enhances cell migrating ability through repressing expression of E-cadherin. (c) 2007 Elsevier Inc. All rights reserved.