title: 53BP1 functions as a tumor suppressor in breast cancer via the inhibition of NF-κB through miR-146a.
abstract: p53-binding protein-1 (53BP1) plays a critical role in cell cycle checkpoint and DNA repair activities. Recently, 53BP1 was recognized as a potential tumor suppressor gene. In this study, we investigated its tumor suppressor function in breast cancer. In clinical samples, we observed a lower level of 53BP1 expression in the cancer lesions than in the matched non-tumor tissues. Furthermore, the 53BP1 level showed a gradual decrease during the progression from precancerous to cancer lesion. Ectopic expression of 53BP1 can significantly inhibit cell proliferation and curb the invasiveness in breast cancer cell lines, whereas knockdown of 53BP1 by RNA interference had the opposite effects. Additionally, 53BP1 markedly inhibited xenograft formation and metastasis of breast cancer cells in nude mice. Both in vitro and in vivo studies revealed that the 53BP1 expression level was inversely correlated to the function of nuclear factor-kappaB (NF-κB), which contributes to the invasion and metastasis of breast cancer. Importantly, the inhibitory effect of 53BP1 on NF-κB activity was shown to be mediated by the upregulation of miR-146a. Together, our findings demonstrated that 53BP1 has a potent tumor suppressor activity in breast cancer, and it may serve as a novel target for breast cancer prevention and treatment.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Wenhua Xi Road No.107, Jinan 250012,  China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.forename: Meena S
authors.initials: MS
authors.lastname: Moran
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000737:chemistry; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C498301:TP53BP1 protein, human; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1