E-Cadherin Is Transcriptionally Activated via Suppression of ZEB1 Transcriptional Repressor by Small RNA-Mediated Gene Silencing

被引：32
作者：
Mazda, Minami [1 ]
Nishi, Kenji [1 ]
Naito, Yuki [1 ]
Ui-Tei, Kumiko [1 ]
机构：
[1] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Tokyo 113, Japan
来源：
PLOS ONE | 2011年 / 6卷 / 12期
关键词：
CRYSTAL-STRUCTURE; INTERFERING RNAS; CANCER-CELLS; SIRNA; EXPRESSION; METHYLATION; ARGONAUTE; DUPLEX; DETERMINANTS; MICRORNAS;
D O I：
10.1371/journal.pone.0028688
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：14
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