https://scholars.lib.ntu.edu.tw/handle/123456789/146430
Title: | MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1{alpha} Expression and Tumor Angiogenesis | Authors: | CHA, SHIH-TING CHEN, PAI-SHENG CHU, CHIA-YU WANG, MING-YANG JENG, YUNG-MING YU, SUNG-LIANG CHEN, JIN-SHING CHANG, KING-JEN JEE, SHIOU-HWA TAN, CHING-TING LIN, MING-TSAN KUO, MIN-LIANG 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 |
Issue Date: | Apr-2010 | Journal Volume: | 70 | Journal Issue: | 7 | Start page/Pages: | 2675-2685 | Source: | CANCER RESEARCH | Abstract: | Hypoxia-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. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/189514 |
Appears in Collections: | 醫學檢驗暨生物技術學系 |
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2010 Cancer Research 70-2675.pdf | 835.79 kB | Adobe PDF | View/Open |
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