Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer.
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.
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
W
W
Kong
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
L
L
He
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
E J
EJ
Richards
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
S
S
Challa
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
C-X
CX
Xu
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J
J
Permuth-Wey
Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J M
JM
Lancaster
Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
D
D
Coppola
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
T A
TA
Sellers
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J Y
JY
Djeu
Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J Q
JQ
Cheng
D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human