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

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 regulat...

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Bibliographic Details
Published in:Angiogenesis (London) 2015-07, Vol.18 (3), p.373-382
Main Authors: Mao, Guangmei, Liu, Yan, Fang, Xi, Liu, Yahan, Fang, Li, Lin, Lianjun, Liu, Xinmin, Wang, Nanping
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Cardiology
Cell Biology
Cell Line, Tumor
Coculture Techniques
Endothelial Cells - metabolism
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Microcirculation
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplasm Transplantation
Neovascularization, Pathologic
Oncology
Ophthalmology
Original Paper
PTEN Phosphohydrolase - metabolism
Wound Healing
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Summary: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.
ISSN:0969-6970
1573-7209
DOI:10.1007/s10456-015-9474-5