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ABSTRACT MicroRNA-155 (miR-155) is frequently upregulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155

in angiogenesis through targeting von Hippel-Lindau (VHL) tumour suppressor in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited human umbilical

vein endothelial cell network formation, proliferation, invasion and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive

angiogenesis, proliferation, tumour necrosis and recruitment of pro-inflammatory cells such as tumour-associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover,

miR-155 expression inversely correlates with VHL expression level and is associated with late-stage, lymph node metastasis and poor prognosis, as well as triple-negative tumour in breast

cancer. These findings indicate that miR-155 has a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive

malignant phenotype, and therefore miR-155 is an important therapeutic target in breast cancer. Access through your institution Buy or subscribe This is a preview of subscription content,

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Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by grants from the National Institute of Health (CA114343 to TAS, CA115308 to JYD, and CA137041 to

JQC) and Florida Bankhead-Coley Cancer Research Program (2BB01 to JQC). AUTHOR INFORMATION Author notes * W Kong and L He: These authors contributed equally to this work. AUTHORS AND

AFFILIATIONS * Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA W Kong, L He, E J Richards, S Challa, C-X Xu & J Q Cheng * Department

of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA J Permuth-Wey & T A Sellers * Department of Women’s Oncology, H. Lee Moffitt Cancer Center

and Research Institute, Tampa, FL, USA J M Lancaster * Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, D Coppola * Department of Immunology, H.

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inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to J Q Cheng. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION

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THIS ARTICLE CITE THIS ARTICLE Kong, W., He, L., Richards, E. _et al._ Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and

triple-negative breast cancer. _Oncogene_ 33, 679–689 (2014). https://doi.org/10.1038/onc.2012.636 Download citation * Received: 06 August 2012 * Revised: 15 November 2012 * Accepted: 16

November 2012 * Published: 28 January 2013 * Issue Date: 06 February 2014 * DOI: https://doi.org/10.1038/onc.2012.636 SHARE THIS ARTICLE Anyone you share the following link with will be able

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initiative KEYWORDS * miR-155 * angiogenesis * VHL * breast cancer * inflammation