title: MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/β-catenin signaling in breast cancer.
abstract: Constitutive activation of the Wnt/β-catenin pathway promotes malignant proliferation and it is inversely correlated with the prognosis of patients with breast cancer. However, mutations in key regulators, such as APC, Axin and β-catenin, contribute to aberrant activation of the Wnt/β-catenin signaling pathway in various cancers, but rarely found in breast cancer, suggesting that other mechanisms might be involved in the activation of Wnt/β-catenin signaling in breast cancer. In the present study, we found that miR-1229 expression was markedly upregulated in breast cancer and associated with poor survival. Overexpressing miR-1229 promoted while inhibiting miR-1229 reduced, proliferation of breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, we found that overexpression of miR-1229 activated the Wnt/β-catenin signaling pathway in breast cancer by directly targeting the multiple important negative regulators of Wnt/β-catenin signaling, including adenomatous polyposis coli (APC), glycogen synthase kinase-3β (GSK-3β), and inhibitor of β-catenin and T cell factor (ICAT). Taken together, our results suggest that miR-1229 plays an important role in promotion breast cancer progression and may represent a novel therapeutic target in breast cancer.
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Zhanyao
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Rehabilitation Medicine, The third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiangxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 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, 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, 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, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
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, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Wnt/β-catenin pathway; breast cancer; miR-1229; proliferation