Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer.
Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer.
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MicroRNA-155(miR-155)在各种类型的人类癌症中经常上调，但其在肿瘤血管生成中的作用尚不清楚。在这里，我们通过靶向乳腺癌中的von Hippel-Lindau肿瘤抑制因子(VHL)来证明miR-155在血管生成中的作用。诱导异位表达miR-155，而敲除miR-155则抑制HUVEC网络的形成、增殖、侵袭和迁移。此外，异位表达miR-155的乳房脂肪垫异种移植导致广泛的血管生成、增殖、肿瘤坏死和促炎细胞(如肿瘤相关巨噬细胞)的募集。VHL的表达可阻断这些miR-155效应。此外，miR-155的表达与VHL的表达水平呈负相关，与乳腺癌的晚期、淋巴结转移、预后不良及三阴性肿瘤有关。这些结果表明miR-155通过下调VHL在肿瘤血管生成中起关键作用，为miR-155表达的肿瘤表现为侵袭性的恶性表型提供了基础，因此miR-155是乳腺癌治疗的重要靶点。
MicroRNA-155 (miR-155) is frequently up-regulated 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 tumour suppressor (VHL) in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited HUVEC 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 plays 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.