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

W Kong, L He, EJ Richards, S Challa, CX Xu… - Oncogene, 2014 - nature.com
W Kong, L He, EJ Richards, S Challa, CX Xu, J Permuth-Wey, JM Lancaster, D Coppola…
Oncogene, 2014nature.com
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 …
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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