E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.

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-complem...

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Main Authors: Minami Mazda, Kenji Nishi, Yuki Naito, Kumiko Ui-Tei
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3244408?pdf=render
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author Minami Mazda
Kenji Nishi
Yuki Naito
Kumiko Ui-Tei
author_facet Minami Mazda
Kenji Nishi
Yuki Naito
Kumiko Ui-Tei
author_sort Minami Mazda
collection DOAJ
description 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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spelling doaj.art-e29742542afa45d7babee12e2315652f2022-12-21T18:34:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2868810.1371/journal.pone.0028688E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.Minami MazdaKenji NishiYuki NaitoKumiko Ui-TeiRNA 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.http://europepmc.org/articles/PMC3244408?pdf=render
spellingShingle Minami Mazda
Kenji Nishi
Yuki Naito
Kumiko Ui-Tei
E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.
PLoS ONE
title E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.
title_full E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.
title_fullStr E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.
title_full_unstemmed E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.
title_short E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing.
title_sort e cadherin is transcriptionally activated via suppression of zeb1 transcriptional repressor by small rna mediated gene silencing
url http://europepmc.org/articles/PMC3244408?pdf=render
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AT yukinaito ecadherinistranscriptionallyactivatedviasuppressionofzeb1transcriptionalrepressorbysmallrnamediatedgenesilencing
AT kumikouitei ecadherinistranscriptionallyactivatedviasuppressionofzeb1transcriptionalrepressorbysmallrnamediatedgenesilencing