, Volume 18, Issue 3, pp 373–382 | Cite as

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

  • Guangmei Mao
  • Yan Liu
  • Xi Fang
  • Yahan Liu
  • Li Fang
  • Lianjun Lin
  • Xinmin Liu
  • Nanping WangEmail author
Original Paper


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.


miR-494 Angiogenesis Non-small cell lung cancer Microvesicle 



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.

Supplementary material

10456_2015_9474_MOESM1_ESM.pdf (160 kb)
Supplementary material 1 (PDF 160 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Guangmei Mao
    • 1
  • Yan Liu
    • 1
  • Xi Fang
    • 1
  • Yahan Liu
    • 1
  • Li Fang
    • 1
  • Lianjun Lin
    • 2
  • Xinmin Liu
    • 2
  • Nanping Wang
    • 1
    • 3
    Email author
  1. 1.Institute of Cardiovascular SciencePeking University Health Science CenterBeijingChina
  2. 2.Geriatric DepartmentPeking University First HospitalBeijingChina
  3. 3.Cardiovascular Research CenterXi’an Jiaotong UniversityXi’anChina

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