Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2

• Published in: Scientific reports 2015-09, Vol.5 (1), p.13827-13827, Article 13827
• Main Authors: Tu, Yingfeng, Liu, Li, Zhao, Dongliang, Liu, Youbin, Ma, Xiaowei, Fan, Yuhua, Wan, Lin, Huang, Tao, Cheng, Zhen, Shen, Baozhong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 60 APPLIED LIFE SCIENCES; 692/308/2056; 692/699/67/2321; AKT protein; Angiogenesis; Animals; Apoptosis; Apoptosis - genetics; BASIC BIOLOGICAL SCIENCES; Breast cancer; Cancer; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Disease Models, Animal; Gene Expression; Human Umbilical Vein Endothelial Cells; Humanities and Social Sciences; Humans; Immunohistochemistry; MAP Kinase Signaling System; Metastases; Mice; MicroRNAs - genetics; miRNA; multidisciplinary; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; raf Kinases - metabolism; Raf protein; RNA Interference; RNA, Messenger - genetics; Rodents; Science; Signal transduction; Transgenic mice; Tumors; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Western blotting; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13827

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.