机构：[1]Center for Molecular Immunology, The Institute of Biophysics, Chinese Academy of Sciences, Beijing 100080, China[2]The Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China[3]Department of Neuronal Surgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China[4]Department of Pathology, Xuzhou Medical College, Xuzhou 221002,China[5]Beijing Tongren Hospital, 100730, China首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Background: Hypoxia inducible factor I is a heterodimeric transcription factor that plays an important role in oxygen homeostasis. A good body of evidence indicates that overexpression of HIF-1 alpha. driven by intratumoral hypoxia can transactivate genes essential for energy metabolism, erythropoiesis, and vascular development, which is directly involved in cancer progression. Overexpressed HIF-1 alpha. also has a considerably reversed clinical correlation with treatment efficacy as well as mortality of cancers. Methods: We took the advantage of the hammerhead ribozyme that specifically targeted 1762-1778 nt of HIF-1 alpha messenger RNA. Results: The designed ribozyme could cleave its substrate HIF-1 alpha messenger RNA in both in vitro and in intracellular cleavage assays. More interesting, the synthetic ribozyme RNA administered to HeLa xenograft large tumor could effectively inhibit its angiogenesis and tumor growth. Conclusion: It is reasonable to speculate that down-regulation of HIF-1 alpha activity could be a potential mechanism useful to prevent survival or angiogenic activity of various solid tumors. (C) 2009 Elsevier Inc. All rights reserved.
基金：
Chinese Academy of Sciences, Beijing, China MOST 973National Basic Research Program of ChinaChinese Academy of Sciences [2002CB513001]; NSFC Outstanding Young Investigator Fellowship, Beijing, China [30025010]; Key Projects of Jiangsu Province Health Department, Nanjing, China [H200104]
