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

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Abstract

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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Acknowledgments

We are grateful for providing the services from the Tissue Bank and RNAi Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital. RNAi reagents were obtained from the National RNAi Core Facility located at the Institute of Molecular Biology/Genomic Research Center, Academia Sinica. This work was supported by grants from the National Science Council (NSC99-2628-B-006-031-MY3, NSC101-2325-B-006-018, and NSC 101-2320-B-006-026-MY3); Department of Health (DOH102-TD-PB-111-TM026 and DOH99-TD-C-111-003); Aim for the Top University Project from National Cheng Kung University, Taiwan.

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Correspondence to Tse-Ming Hong.

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Yi-Ying Wu and Yuh-Ling Chen have contributed equally to this work.

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Wu, YY., Chen, YL., Jao, YC. et al. miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1. Angiogenesis 17, 247–260 (2014). https://doi.org/10.1007/s10456-013-9394-1

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