Key Laboratory of Molecular Biophysics of the Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, PR China.
Cancer Lett. 2013 Jun 10;333(2):159-69. doi: 10.1016/j.canlet.2013.01.028. Epub 2013 Jan 22.
FGF2 and VEGFA are the two most potent angiogenic factors. Here we report that miR-503 can simultaneously down-regulate FGF2 and VEGFA. The expression of miR-503 is repressed in HCC cells and primary tumors due to a potential epigenetic mechanism. Overexpression of miR-503 reduced tumor angiogenesis in vitro and in vivo. We also found that miR-503 expression was down-regulated by hypoxia through HIF1α. These results identify a miRNA that targets both FGF2 and VEGFA in cancers, demonstrate the anti-angiogenesis role of miR-503 in tumorigenesis, and provide a novel mechanism for hypoxia-induced FGF2 and VEGFA through HIF1α-mediated inhibition of miR-503.
FGF2 和 VEGFA 是两种最有效的血管生成因子。在这里，我们报告 miR-503 可以同时下调 FGF2 和 VEGFA。由于潜在的表观遗传机制，miR-503 的表达在 HCC 细胞和原发性肿瘤中受到抑制。miR-503 的过表达减少了体外和体内的肿瘤血管生成。我们还发现 miR-503 的表达受缺氧通过 HIF1α 下调。这些结果确定了一种在癌症中靶向 FGF2 和 VEGFA 的 miRNA，证明了 miR-503 在肿瘤发生中的抗血管生成作用，并提供了一种通过 HIF1α 介导的 miR-503 抑制来诱导缺氧诱导的 FGF2 和 VEGFA 的新机制。
