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

• Published in: Scientific reports Vol. 7; no. 1; pp. 8967 - 14
• Main Authors: Zheng, Liduan, Chen, Yajun, Ye, Lin, Jiao, Wanju, Song, Huajie, Mei, Hong, Li, Dan, Yang, Feng, Li, Huanhuan, Huang, Kai, Tong, Qiangsong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/109; 13/44; 13/89; 38/15; 38/77; 45/22; 64/60; 692/4028/67/1504/1829; 692/4028/67/395; Animals; Argonaute 2 protein; Cell Line, Tumor; Computational Biology; Disease Models, Animal; Down-Regulation; Gastric cancer; Humanities and Social Sciences; Humans; Lysine; Matrix metalloproteinase; Matrix Metalloproteinase 14 - biosynthesis; Metalloproteinase; Methyltransferase; Mice, Inbred BALB C; MicroRNAs - metabolism; miRNA; multidisciplinary; Neoplasm Transplantation; Science; Science (multidisciplinary); Stomach Neoplasms - pathology; Transcription; Tumorigenesis; YY1 Transcription Factor - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09271-5

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.