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Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer

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Abstract

Angiogenesis, a crucial step in tumor growth and metastasis, is regulated by various pro- or anti-angiogenic factors. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, roles of tumor-derived microRNAs in regulating tumor vascularization remain to be elucidated. In this study, we found that delivery of miR-494 into human vascular endothelial cells (ECs) enhanced the EC migration and promoted angiogenesis. The angiogenic effect of miR-494 was mediated by the targeting of PTEN and the subsequent activation of Akt/eNOS pathway. Importantly, co-culture experiments demonstrated that a lung cancer cell line, A549, secreted and delivered miR-494 into ECs via a microvesicle-mediated route. In addition, we found that the expression of miR-494 was induced in the tumor cells in response to hypoxia, likely via a HIF-1α-mediated mechanism. Furthermore, a specific miR-494 antagomiR effectively inhibited angiogenesis and attenuated the growth of tumor xenografts in nude mice. Taken together, these results demonstrated that miR-494 is a novel tumor-derived paracrine signal to promote angiogenesis and tumor growth under hypoxic condition.

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Acknowledgments

This work was supported by grants from the National Science Foundation of China (#30881220108005, 31430045 and 81470373) and the Provincial Office of Science and Technology, Shaanxi (2011KTCQ03-14).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute of Cardiovascular Science, Peking University Health Science Center, 38 Xueyuan Rd, Beijing, 100191, China

    Guangmei Mao, Yan Liu, Xi Fang, Yahan Liu, Li Fang & Nanping Wang

  2. Geriatric Department, Peking University First Hospital, Beijing, China

    Lianjun Lin & Xinmin Liu

  3. Cardiovascular Research Center, Xi’an Jiaotong University, Xi’an, China

    Nanping Wang

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  1. Guangmei Mao
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  2. Yan Liu
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  3. Xi Fang
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Correspondence to Nanping Wang.

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Mao, G., Liu, Y., Fang, X. et al. Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer. Angiogenesis 18, 373–382 (2015). https://doi.org/10.1007/s10456-015-9474-5

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