53BP1 suppresses epithelial–mesenchymal transition by downregulating ZEB1 through microRNA‐200b/429 in breast cancer. Issue 8 (14th July 2015)

• Record Type: Journal Article
• Authors: Kong, Xiangnan; Ding, Xia; Li, Xiaoyan; Gao, Sumei; Yang, Qifeng
• Is Part Of: Cancer science. Volume 106:Issue 8(2015:Aug.)
• Page Start: 982
• Page End: 989
• Publication Date: 2015-07-14
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12699
• Languages: English
• ISSNs: 1347-9032

Abstract

<abstract abstract-type="main" id="cas12699-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Epithelial–mesenchymal transition (EMT) is an important mechanism of cancer invasion and metastasis. Although p53 binding protein 1 (<italic>53BP1</italic>) has been implicated in several biological processes, its function in EMT of human cancers has not yet been reported. Here, we show that <italic>53BP1</italic> negatively regulated EMT by modulating <italic>ZEB1</italic> through targeting microRNA (miR)‐200b and miR‐429. Furthermore, <italic>53BP1</italic> promoted <italic>ZEB1</italic>‐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 <italic>53BP1</italic> 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 <italic>ZEB1</italic> expression and decreased E‐cadherin expression with the downregulation of <italic>53BP1</italic>. In 18 clinical tissue samples, expression of <italic>53BP1</italic> was positively correlated with miR‐200b and mir‐429 and negatively correlated with <italic>ZEB1</italic>. It was also found that <italic>53BP1</italic> was associated with lymph node metastasis. Taken together, these results suggest that <italic>53BP1</italic> 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 <italic>ZEB1</italic>.</p> </abstract>