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

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
12
Identifiers
DOI: 10.1371/journal.pone.0028688
Source
Legacy
Keywords
  • Research Article
  • Biology
  • Biophysics
  • Nucleic Acids
  • Rna
  • Rna Interference
  • Computational Biology
  • Macromolecular Structure Analysis
  • Rna Structure
  • Developmental Biology
  • Stem Cells
  • Embryonic Stem Cells
  • Stem Cell Lines
  • Genetics
  • Epigenetics
  • Gene Expression
  • Rna Stability
  • Molecular Cell Biology
  • Cellular Types

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 3′ 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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