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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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) |
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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 |
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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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