期刊
ANGIOGENESIS
卷 17, 期 1, 页码 247-260出版社
SPRINGER
DOI: 10.1007/s10456-013-9394-1
关键词
miR-320; Angiogenesis; Neuropilin 1; Oral cancer
资金
- National Science Council [NSC99-2628-B-006-031-MY3, NSC101-2325-B-006-018, NSC 101-2320-B-006-026-MY3]
- Department of Health [DOH102-TD-PB-111-TM026, DOH99-TD-C-111-003]
- Aim for the Top University Project from National Cheng Kung University, Taiwan
Tumor angiogenesis is a critical process during cancer progression that modulates tumor growth and metastasis. Here, we identified an anti-angiogenic microRNA, miR-320, which is decreased in oral squamous cell carcinoma (OSCC) cell lines and tumor tissues from OSCC patients, down-regulated in blood vessels and inversely correlated with vascularity in OSCC tissues. Neuropilin 1 (NRP1), an important regulator of angiogenesis, was found to be a target of miR-320. The 3'-untranslated region of NRP1 mRNA contains multiple miR-320 binding sites, and its expression was regulated by miR-320. By administering either miR-320 precursor or antagonist, we found that miR-320 suppressed the migration, adhesion and tube formation of vascular endothelial cells. Knockdown of NRP1 abolished antagomiR-320-induced cell migration. Additionally, miR-320 expression was regulated by hypoxia in growth factor-deficient conditions by the hypoxia-inducible factor 1-alpha. Furthermore, lentivirus carrying the miR-320 precursor suppressed the tumorigenicity of OSCC cells and tumor angiogenesis in vivo. Taken together, these data show that miR-320 regulates the function of vascular endothelial cells by targeting NRP1 and has the potential to be developed as an anti-angiogenic or anti-cancer drug.
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