Open Access53 BP 1 suppresses epithelial–mesenchymal transition by downregulating ZEB 1 through micro RNA ‐200b/429 in breast cancer
Author(s) -
Kong Xiangnan,
Ding Xia,
Li Xiaoyan,
Gao Sumei,
Yang Qifeng
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12699
Subject(s) - downregulation and upregulation , epithelial–mesenchymal transition , cancer research , microrna , cadherin , metastasis , breast cancer , cancer , chemistry , biology , microbiology and biotechnology , gene , cell , genetics , biochemistry
Epithelial–mesenchymal transition ( EMT ) is an important mechanism of cancer invasion and metastasis. Although p53 binding protein 1 ( 53 BP 1 ) has been implicated in several biological processes, its function in EMT of human cancers has not yet been reported. Here, we show that 53 BP 1 negatively regulated EMT by modulating ZEB 1 through targeting micro RNA (miR)‐200b and miR‐429. Furthermore, 53 BP 1 promoted ZEB 1 ‐mediated upregulation of E‐cadherin and also inhibited the expressions of mesenchymal markers, leading to increased migration and invasion in MDA ‐ MB ‐231 breast cancer cells. Consistently, in MCF ‐7 breast cancer cells, low 53 BP 1 expression reduced E‐cadherin expression, resulting in increased migration and invasion. These effects were reversed by miR‐200b and miR‐429 inhibition or overexpression. Sections of tumor xenograft model showed increased ZEB 1 expression and decreased E‐cadherin expression with the downregulation of 53 BP 1 . In 18 clinical tissue samples, expression of 53 BP 1 was positively correlated with miR‐200b and mir‐429 and negatively correlated with ZEB 1 . It was also found that 53 BP 1 was associated with lymph node metastasis. Taken together, these results suggest that 53 BP 1 functioned as a tumor suppressor gene by its novel negative control of EMT through regulating the expression of miR‐200b/429 and their target gene ZEB 1 .