e-cadherin is transcriptionally activated via suppression of zeb1 transcriptional repressor by small rna-mediated gene silencing钙粘蛋白是通过抑制转录激活zeb1转录抑制因子的小rna介导的基因沉默.pdfVIP

E-Cadherin Is Transcriptionally Activated via Suppression of ZEB1 Transcriptional Repressor by Small RNA- Mediated Gene Silencing Minami Mazda, Kenji Nishi, Yuki Naito, Kumiko Ui-Tei* Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan Abstract RNA activation has been reported to be induced by small interfering RNAs (siRNAs) that act on the promoters of several genes containing E-cadherin. In this study, we present an alternative mechanism of E-cadherin activation in human PC-3 cells by siRNAs previously reported to possess perfect-complementary sequences to E-cadherin promoter. We found that activation of E-cadherin can be also induced via suppression of ZEB1, which is a transcriptional repressor of E-cadherin, by seed-dependent silencing mechanism of these siRNAs. The functional seed-complementary sites of the siRNAs were found in the coding region in addition to the 39 untranslated region of ZEB1 mRNA. Promoter analyses indicated that E-boxes, which are ZEB1-binding sites, in the upstream promoter region are indispensable for E-cadherin transcription by the siRNAs. Thus, the results caution against ignoring siRNA seed-dependent silencing effects in genome-wide transcriptional regulation. In addition, members of miR-302/372/373/520 family, which have the same seed sequences with one of the siRNAs containing perfect-complementarity to E-cadherin promoter, are also found to activate E-cadherin transcription. Thus, E-cadherin could be upregulated by the suppression of ZEB1 transcriptional repressor by miRNAs in vivo. Citation: Mazda M, Nishi K, Naito Y, Ui-Tei K (2011) E-Cadherin Is Transcriptionally Activated via Suppression of ZEB1 Transcriptional Repressor by Small RNA- Mediated Gene Silencing. PLoS ONE 6(12): e28688. doi:10.1371/journal.pone.0028688 Editor: Akio K