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Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer

Oncogene volume 33, pages 679–689 (2014)Cite this article

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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.

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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).

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Author notes

  1. W Kong and L He: These authors contributed equally to this work.

Authors and Affiliations

  1. 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

  2. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    J Permuth-Wey & T A Sellers

  3. Department of Women’s Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    J M Lancaster

  4. Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA,

    D Coppola

  5. Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA,

    J Y Djeu

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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

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