醫學檢驗暨生物技術學系醫學系耳鼻喉科醫學系皮膚科CHA, SHIH-TINGSHIH-TINGCHACHEN, PAI-SHENGPAI-SHENGCHENCHU, CHIA-YUCHIA-YUCHUWANG, MING-YANGMING-YANGWANGJENG, YUNG-MINGYUNG-MINGJENGYU, SUNG-LIANGSUNG-LIANGYUCHEN, JIN-SHINGJIN-SHINGCHENCHANG, KING-JENKING-JENCHANGJEE, SHIOU-HWASHIOU-HWAJEETAN, CHING-TINGCHING-TINGTANLIN, MING-TSANMING-TSANLINKUO, MIN-LIANGMIN-LIANGKUO查詩婷陳百昇朱家瑜王明暘鄭永銘俞松良陳晉興張金堅紀秀華譚慶鼎林明燦郭明良2010-07-162018-07-062010-07-162018-07-062010-04http://ntur.lib.ntu.edu.tw//handle/246246/189514Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is widely considered to be one of the key regulators of tumor angiogenesis . The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1 alpha, acting through direct binding to the HIF-1 alpha 3' untranslated region and leading to reduced tumor angiogenesis . Overexpression of miR-519c resulted in a significant decrease of HIF-1 alpha protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1 alpha protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1 alpha-mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR-519c- overexpressing cells exhibited dramatically reduced HIF-1 alpha levels, followed by suppressed tumor angiogenesis , growth, and metastasis. In addition, we found that hepatocyte growth factor (HGF), a known HIF-1 alpha inducer, reduced the miR-519c levels through an Akt-dependent pathway. This regulation was post-transcriptional and may be mediated by suppression of miR-519c maturation. Taken together, our findings provide the first evidence that miR- 519c is a pivotal regulator of tumor angiogenesis and that microenvironmental HGF contributes to regulating miR-519c biogenesis in cancer cells.855849 bytesapplication/pdfen-US[SDGs]SDG3http://ntur.lib.ntu.edu.tw/bitstream/246246/189514/1/2010 Cancer Research 70-2675.pdf