中文摘要：

血管生成素（angiogenin,ANG）能有效促进血管生成和肿瘤细胞增殖,在肿瘤发生发展中起重要作用.其主要分子机制是通过核转位和激活PI3K/AKT/m TOR信号通路,刺激r RNA转录和核糖体生成.ANG也被发现在肌萎缩侧索硬化症（ALS）和帕金森病（PD）患者中存在基因编码区的功能突变,表明其在运动神经元生理方面发挥作用,其缺陷是神经退行性疾病的一个危险因素.核糖核酸酶抑制因子（ribonuclease inhibitor,RI）是胞内酸性蛋白质,由460个氨基酸残基组成,分子质量约为50 k D,当其与核糖核酸酶A（RNase A）结合形成复合物后,可抑制RNase A的90%以上活性,从而有效调节细胞内RNA水平.ANG具有低核糖核酸酶活性,是RNase超家族一员,与RNase A有着高度保守的同源顺序.序列、结构和酶学等分析表明,RI也能够与ANG紧密结合,且得到体外实验的证明.研究发现,RI具抑癌基因功能;RI与ANG在细胞内共定位;Co-IP和GST pull-down证实其相互作用,获取了RI与ANG在体内结合的直接证据;RI与AKT磷酸化表达负相关.在膀胱癌细胞及临床标本中证实了RI与ANG和PI3K/AKT通路分子表达的相关性及与肿瘤细胞生长与转移的关系.在细胞和动物模型研究表明,RI调节ANG活性的功能及其分子机制,即RI通过结合ANG而封锁其核转位和调控PI3K/AKT/m TOR信号通路及其相关通路交互应答（cross-talk）的能力,从而抑制肿瘤生长及转移.RI是一个有希望的抗肿瘤蛋白新药和血管生成抑制剂,可望成为基因治疗的靶基因.

英文摘要：

Angiogenin （ANG） was recently shown to promote angiogenesis and tumor cell proliferation, which are important for the development of cancers. ANG stimulates ribosomal RNA transcription and the ribosome biogenesis through the activation of nuclear translocation and PI3K/Akt/mTOR signaling pathway. ANG mutations in the gene encoding region were found in amyotrophic lateral sclerosis （ALS） and Parkinson＇ s disease （PD） patients, suggesting its possible role in the physiology of motor neurons as a risk factor for neurodegenerative diseases. Ribonuclease inhibitor （R1） is an intracellular acidic protein of 460 amino acid residues with a molecular weight about 50kD. RI and ribonuclease A （RNase A） jointly inhibit RNase activity and regulate intracellular RNA levels. ANG is a member of the RNase superfamily and is the only identified human angiogenic factor with a ribonucleolytic activity. ANG and RNase A share conserved homologous sequence. RI has a tumor suppressor function, where tightly binds to and colocalizes with ANG in GST pull-down/co-immunoprecipitation assays and microscopy. RI negatively correlated to AKT phosphorylation in bladder cancer specimen and connected to tumor growth and metastasis. RI is an important ANG regulator and could be a perspective anti-tumor target for gene therapy.