Reactive oxygen species regulate ERBB2 and ERBB3 expression via miR-199a/125b and DNA methylation

被引：111

作者：

He, Jun ^{[1
,2
,3
]}

Xu, Qing ^{[1
,2
]}

Jing, Yi ^{[3
]}

Agani, Faton ^{[3
]}

Qian, Xu ^{[1
,2
]}

Carpenter, Richard ^{[3
]}

Li, Qi ^{[1
,2
]}

Wang, Xin-Ru ^{[1
,2
]}

Peiper, Stephen S. ^{[3
]}

Lu, Zhimin ^{[4
,5
]}

Liu, Ling-Zhi ^{[3
]}

Jiang, Bing-Hua ^{[1
,2
,3
]}

机构：

[1] Nanjing Med Univ, Ctr Canc, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Ctr Canc, Dept Pathol, Nanjing 210029, Jiangsu, Peoples R China

[3] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA

[4] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

来源：

EMBO REPORTS | 2012年 / 13卷 / 12期

基金：

中国国家自然科学基金;

关键词：

miR-199a; miR-125b; ERBB2/3; ROS; DNA methylation; GROWTH-FACTOR RECEPTOR; OXIDATIVE STRESS; CANCER; MICRORNAS; GEFITINIB; MIR-125B; TARGETS; HER3;

D O I：

10.1038/embor.2012.162

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Overexpression of ERBB2 or ERBB3 is associated with cancer development and poor prognosis. In this study, we show that reactive oxygen species (ROS) induce both ERBB2 and ERBB3 expression in vitro and in vivo. We also identify that miR-199a and miR-125b target ERBB2 and/or ERBB3 in ovarian cancer cells, and demonstrate that ROS inhibit miR-199a and miR-125b expression through increasing the promoter methylation of the miR-199a and miR-125b genes by DNA methyltransferase 1. These findings reveal that ERBB2 and ERBB3 expression is regulated by ROS via miR-199a and miR-125b downregulation and DNA hypermethylation.

引用

页码：1116 / 1122

页数：7

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