title: 53BP1 suppresses epithelial-mesenchymal transition by downregulating ZEB1 through microRNA-200b/429 in breast cancer.
abstract: 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.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, China.|Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C533896:MIRN200 microRNA, human; C546363:MIRN429 microRNA, human; D035683:MicroRNAs; C498301:TP53BP1 protein, human; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: 53BP1; ZEB1; breast cancer; epithelial-mesenchymal transition; microRNA