NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2

被引：87

作者：

Hu, Pengnan ^{[1
,2
,3
]}

Chu, Junjun ^{[1
,3
]}

Wu, Yanqing ^{[1
,3
]}

Sun, Lijuan ^{[1
,3
]}

Lv, Xiaobin ^{[1
,3
]}

Zhu, Yinghua ^{[1
,3
]}

Li, Jingjing ^{[1
,3
]}

Guo, Qiannan ^{[1
,3
]}

Gong, Chang ^{[1
,3
]}

Liu, Bodu ^{[1
,2
,3
]}

Su, Shicheng ^{[1
,3
]}

机构：

[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510275, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Key Lab Gene Engn,Minist Educ, Guangzhou 510275, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510275, Guangdong, Peoples R China

来源：

ONCOTARGET | 2015年 / 6卷 / 32期

基金：

中国博士后科学基金;

关键词：

LncRNA; NBAT1; breast cancer; metastasis; LONG NONCODING RNA; MAMMARY EPITHELIAL-CELLS; E-CADHERIN; EZH2; PROLIFERATION; EXPRESSION; HOTAIR; GENES; WNT; PHOSPHORYLATION;

D O I：

10.18632/oncotarget.5609

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Long noncoding RNA NBAT1 (neuroblastoma associated transcript 1) regulates cell proliferation and invasion by interacting with PRC2 (polycomb repressive complex 2) member EZH2 (enhancer of zeste 2). Decreased expression of NBAT1 is associated with poor clinical outcome in neuroblastomas. However, the roles of NBAT1 in other cancers remain unknown. Here, we report that NBAT1 is down-regulated in various types of cancer. Particularly, reduced NBAT1 in breast cancer is associated with tumor metastasis and poor patient prognosis. In vitro, ectopic NBAT1 inhibits migration and invasion of breast cancer cells. Mechanistic study shows that NBAT1 is associated with PRC2 member EZH2 and regulates global gene expression profile. Among them, DKK1 (dickkopf WNT signaling pathway inhibitor 1) is found to be regulated by NBAT1 in a PRC2 dependent manner, and is responsible for NBAT1's effects in inhibiting migration and invasion of breast cancer cells. Taken together, our study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis.

引用

页码：32410 / 32425

页数：16

共 38 条

[1] EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast [J].