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- Title
Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2.
- Authors
Tu, Yingfeng; Liu, Li; Zhao, Dongliang; Liu, Youbin; Ma, Xiaowei; Fan, Yuhua; Wan, Lin; Huang, Tao; Cheng, Zhen; Shen, Baozhong
- Abstract
Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.
- Subjects
MICRORNA; TRANSGENIC mice; NEOVASCULARIZATION; GENETIC overexpression; LABORATORY mice; VASCULAR endothelial growth factor receptors
- Publication
Scientific Reports, 2015, p13827
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep13827