title: miR-892b Silencing Activates NF-κB and Promotes Aggressiveness in Breast Cancer.
abstract: The strength and duration of NF-κB signaling is tightly controlled at multiple levels under physiologic conditions, but the mechanism underlying constitutive activation of the NF-κB pathway in cancer remains unclear. In this study, we investigated miRNA-mediated regulation of the NF-κB cascade in breast cancer. We report that miR-892b expression was significantly downregulated in human breast cancer specimens and correlated with poor patient survival. Overexpression of miR-892b in breast cancer cells significantly decreased tumor growth, metastatic capacity, and the ability to induce angiogenesis, whereas miR-892b depletion enhanced these properties, in vitro and in vivo. Furthermore, we demonstrate that miR-892b attenuated NF-κB signaling by directly targeting and suppressing multiple mediators of NF-κB, including TRAF2, TAK1, and TAB3, and thus, miR-892b silencing in breast cancer cells sustains NF-κB activity. Moreover, miR-892b downregulation was attributed to aberrant hypermethylation of its promoter. Taken together, our results provide insight into a new mechanism by which NF-κB signaling becomes constitutively activated in breast cancer and suggest a tumor-suppressive role for miR-829b, prompting further investigation into miRNA mimics for cancer therapy.
authors.affiliation: Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong, China. State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Vascular and Breast Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Fangyong
authors.initials: F
authors.lastname: Lei
authors.affiliation: Department of Pathogen Biology and Immunology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiangxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Geyan
authors.initials: G
authors.lastname: Wu
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Lixue
authors.initials: L
authors.lastname: Cao
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Aibin
authors.initials: A
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, China. songlb@sysucc.org.cn lijun37@mail.sysu.edu.cn.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. songlb@sysucc.org.cn lijun37@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D025821:Polyubiquitin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology
chemical_list: C574666:MIRN892 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D025821:Polyubiquitin