53BP1 suppresses epithelial-mesenchymal transition by downregulating ZEB1 through microRNA-200b/429 in breast cancer.

Epithelial-mesenchymal transition (EMT) is an important mechanism of cancer invasion and metastasis. Although p53 binding protein 1 (53BP1) has been implicated in several biological processes, its function in EMT of human cancers has not yet been reported. Here, we show that 53BP1 negatively regulated EMT by modulating ZEB1 through targeting microRNA (miR)-200b and miR-429. Furthermore, 53BP1 promoted ZEB1-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 53BP1 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 ZEB1 expression and decreased E-cadherin expression with the downregulation of 53BP1. In 18 clinical tissue samples, expression of 53BP1 was positively correlated with miR-200b and mir-429 and negatively correlated with ZEB1. It was also found that 53BP1 was associated with lymph node metastasis. Taken together, these results suggest that 53BP1 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 ZEB1.

Kong X ，Ding X ，Li X ，Gao S ，Yang Q ... -  《-》

Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer.

Lee JY ，Park MK ，Park JH ，Lee HJ ，Shin DH ，Kang Y ，Lee CH ，Kong G ... -  《-》

MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma.

Kurashige J ，Kamohara H ，Watanabe M ，Hiyoshi Y ，Iwatsuki M ，Tanaka Y ，Kinoshita K ，Saito S ，Baba Y ，Baba H ... -  《-》

Dual regulation by microRNA-200b-3p and microRNA-200b-5p in the inhibition of epithelial-to-mesenchymal transition in triple-negative breast cancer.

Rhodes LV ，Martin EC ，Segar HC ，Miller DF ，Buechlein A ，Rusch DB ，Nephew KP ，Burow ME ，Collins-Burow BM ... -  《Oncotarget》

Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma.

Cong N ，Du P ，Zhang A ，Shen F ，Su J ，Pu P ，Wang T ，Zjang J ，Kang C ，Zhang Q ... -  《-》