miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression

Abstract Recent evidence shows the emerging roles of promoter-targeting endogenous microRNAs (miRNAs) in regulating gene transcription. However, miRNAs affecting the transcription of matrix metalloproteinase 14 (MMP-14) in gastric cancer remain unknown. Herein, through integrative mining of public d...

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Autores principales: Liduan Zheng, Yajun Chen, Lin Ye, Wanju Jiao, Huajie Song, Hong Mei, Dan Li, Feng Yang, Huanhuan Li, Kai Huang, Qiangsong Tong
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/ead896ab73b9497c8ca962a56efd3362
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spelling oai:doaj.org-article:ead896ab73b9497c8ca962a56efd33622021-12-02T16:07:01ZmiRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression10.1038/s41598-017-09271-52045-2322https://doaj.org/article/ead896ab73b9497c8ca962a56efd33622017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09271-5https://doaj.org/toc/2045-2322Abstract Recent evidence shows the emerging roles of promoter-targeting endogenous microRNAs (miRNAs) in regulating gene transcription. However, miRNAs affecting the transcription of matrix metalloproteinase 14 (MMP-14) in gastric cancer remain unknown. Herein, through integrative mining of public datasets, we identified the adjacent targeting sites of Yin Yang 1 (YY1) and miRNA-584-3p (miR-584-3p) within MMP-14 promoter. We demonstrated that YY1 directly targeted the MMP-14 promoter to facilitate its expression in gastric cancer cells. In contrast, miR-584-3p recognized its complementary site within MMP-14 promoter to suppress its expression. Mechanistically, miR-584-3p interacted with Argonaute 2 to recruit enhancer of zeste homolog 2 and euchromatic histone lysine methyltransferase 2, resulting in enrichment of repressive epigenetic markers and decreased binding of YY1 to MMP-14 promoter. miR-584-3p inhibited the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cells through repressing YY1-facilitated MMP-14 expression. In clinical gastric cancer tissues, the expression of YY1 and miR-584-3p was positively or negatively correlated with MMP-14 levels. In addition, miR-584-3p and YY1 were independent prognostic factors associated with favorable and unfavorable outcome of gastric cancer patients, respectively. These data demonstrate that miR-584-3p directly targets the MMP-14 promoter to repress YY1-facilitated MMP-14 expression and inhibits the progression of gastric cancer.Liduan ZhengYajun ChenLin YeWanju JiaoHuajie SongHong MeiDan LiFeng YangHuanhuan LiKai HuangQiangsong TongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Liduan Zheng
Yajun Chen
Lin Ye
Wanju Jiao
Huajie Song
Hong Mei
Dan Li
Feng Yang
Huanhuan Li
Kai Huang
Qiangsong Tong
miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression
description Abstract Recent evidence shows the emerging roles of promoter-targeting endogenous microRNAs (miRNAs) in regulating gene transcription. However, miRNAs affecting the transcription of matrix metalloproteinase 14 (MMP-14) in gastric cancer remain unknown. Herein, through integrative mining of public datasets, we identified the adjacent targeting sites of Yin Yang 1 (YY1) and miRNA-584-3p (miR-584-3p) within MMP-14 promoter. We demonstrated that YY1 directly targeted the MMP-14 promoter to facilitate its expression in gastric cancer cells. In contrast, miR-584-3p recognized its complementary site within MMP-14 promoter to suppress its expression. Mechanistically, miR-584-3p interacted with Argonaute 2 to recruit enhancer of zeste homolog 2 and euchromatic histone lysine methyltransferase 2, resulting in enrichment of repressive epigenetic markers and decreased binding of YY1 to MMP-14 promoter. miR-584-3p inhibited the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cells through repressing YY1-facilitated MMP-14 expression. In clinical gastric cancer tissues, the expression of YY1 and miR-584-3p was positively or negatively correlated with MMP-14 levels. In addition, miR-584-3p and YY1 were independent prognostic factors associated with favorable and unfavorable outcome of gastric cancer patients, respectively. These data demonstrate that miR-584-3p directly targets the MMP-14 promoter to repress YY1-facilitated MMP-14 expression and inhibits the progression of gastric cancer.
format article
author Liduan Zheng
Yajun Chen
Lin Ye
Wanju Jiao
Huajie Song
Hong Mei
Dan Li
Feng Yang
Huanhuan Li
Kai Huang
Qiangsong Tong
author_facet Liduan Zheng
Yajun Chen
Lin Ye
Wanju Jiao
Huajie Song
Hong Mei
Dan Li
Feng Yang
Huanhuan Li
Kai Huang
Qiangsong Tong
author_sort Liduan Zheng
title miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression
title_short miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression
title_full miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression
title_fullStr miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression
title_full_unstemmed miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1- facilitated MMP-14 expression
title_sort mirna-584-3p inhibits gastric cancer progression by repressing yin yang 1- facilitated mmp-14 expression
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/ead896ab73b9497c8ca962a56efd3362
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