Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2.
Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2.
复制标题
miRNA-497 的过表达通过靶向 VEGFR2 抑制肿瘤血管生成
DOI：
10.1038/srep13827
复制
发表时间：
2015-09-08
影响因子：
4.6
通讯作者：
Shen B
中科院分区：
文献类型：
--
作者：
Tu Y;Liu L;Zhao D;Liu Y;Ma X;Fan Y;Wan L;Huang T;Cheng Z;Shen B
最近的研究报道miR-497在多种癌症中表现出抑制作用。然而，miR-497是否参与抑制血管生成，这对肿瘤生长和转移至关重要，仍然是未知的。本研究旨在探讨miR-497在肿瘤血管生成中的潜在作用。本研究采用MTT法和TUNEL法检测miR-497对HUVECs增殖和凋亡的影响，探讨miR-497在HUVECs中的作用。采用蛋白质印迹法（WB）验证miR-497的下游靶标。此外，为了揭示miR-497在血管生成中的作用，我们用miR-497模拟物处理VEGFR2-luc转基因小鼠，并应用活体生物发光成像（BLI）监测肿瘤血管生成和生长。结果表明，miR-497的过表达对VEGFR2的激活及下游Raf/MEK/ERK信号通路有抑制作用。此外，miR-497过表达可通过靶向VEGFR2和下游PI3K/AKT信号通路诱导HUVECs凋亡。此外，miR-497在VEGFR2-luc乳腺肿瘤模型中表现出抗血管生成和抗肿瘤作用，通过BLI、WB和免疫组织化学分析证实。综上所述，miR-497通过靶向VEGFR2抑制肿瘤血管生成和生长，表明miR-497可以作为潜在的癌症治疗候选药物进行探索。
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 byin vivobioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathwaysin vitroandin 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.