53 BP 1 suppresses epithelial–mesenchymal transition by downregulating ZEB 1 through micro RNA ‐200b/429 in breast cancer

• Published in: Cancer science Vol. 106; no. 8; pp. 982 - 989
• Main Authors: Kong, Xiangnan, Ding, Xia, Li, Xiaoyan, Gao, Sumei, Yang, Qifeng
• Format: Journal Article
• Language: English
• Published: Tokyo John Wiley & Sons, Inc 01.08.2015
• Subjects: Biotechnology; Breast cancer; Lymph nodes; Lymphatic system; Mesenchyme; Metastases; Metastasis; MicroRNAs; miRNA; p53 Protein; Plasmids; Proteins; Tumor suppressor genes; Tumors; Xenografts; United States > US; China
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12699

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 .