MicroRNA 519c Suppresses Hypoxia Inducible Factor 1α Expression and Tumor Angiogenesis英文文献.pdfVIP

Microenvironment and Immunology Cancer Research MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis 1 1,7 1 1,4 1,3,7 Shih-Ting Cha , Pai-Sheng Chen , Gunnar Johansson , Chia-Yu Chu , Ming-Yang Wang , 5 2 3 3,7 4 Yung-Ming Jeng , Sung-Liang Yu , Jin-Shing Chen , King-Jen Chang , Shiou-Hwa Jee , 6 3 1,5 Ching-Ting Tan , Ming-Tsan Lin , and Min-Liang Kuo Abstract Hypoxia-inducible factor-1α (HIF-1α) is widely considered to be one of the key regulators of tumor angio- genesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Here- in, we have identified miR-519c as a hypoxia-independent regulator of HIF-1α, acting through direct binding to the HIF-1α 3′ untranslated region and leading to reduced tumor angiogenesis. Overexpression of miR-519c resulted in a significant decrease of HIF-1α protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1α protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1α–mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR