miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1

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• 作者：Yi-Ying Wu (1)
  Yuh-Ling Chen (2) (3)
  Yun-Chia Jao (3)
  I-Shan Hsieh (2)
  Kung-Chao Chang (4)
  Tse-Ming Hong (1)
  
• 关键词：miR ; 320 ; Angiogenesis ; Neuropilin 1 ; Oral cancer
• 刊名：Angiogenesis
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：17
• 期：1
• 页码：247-260
• 全文大小：882 KB
• 作者单位：Yi-Ying Wu (1)
  Yuh-Ling Chen (2) (3)
  Yun-Chia Jao (3)
  I-Shan Hsieh (2)
  Kung-Chao Chang (4)
  Tse-Ming Hong (1)
  
  1. Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
  2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
  3. Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
  4. Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
  
• ISSN：1573-7209

文摘

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.