核糖修饰小激活RNA分子治疗膀胱癌的体内实验研究

项目名称： 核糖修饰小激活RNA分子治疗膀胱癌的体内实验研究

项目编号： No.81201767

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 白宇

作者单位： 昆明医科大学

项目金额： 23万元

中文摘要： 膀胱移行细胞癌是我国泌尿系统最常见的恶性肿瘤，利用新手段新方法进行膀胱癌治疗的研究十分必要。本人所参加的研究组自2007 年初起一直致力于RNA 诱导的基因激活机制及其在泌尿系肿瘤治疗中应用的研究。本研究的目标是核糖修饰小激活RNA 分子（saRNAs）全身给药治疗膀胱癌的体内方案。研究内容包括首先筛选出不影响激活效应的核糖修饰saRNAs,并评估其体外血清稳定性；应用体内试验评价核糖修饰saRNAs 对裸鼠异种移植膀胱癌模型的肿瘤生长及转移抑制效果，筛选出抗肿瘤作用最强的核糖修饰saRNAs 分子；进一步评估该核糖修饰saRNAs 相对于未修饰saRNAs 在体内的药物代谢学特点。本研究将为RNAs 激活技术的进一步临床研究提供理论基础。

中文关键词： 核糖修饰；小激活RNA；膀胱癌；；

英文摘要： Bladder cancer is the most common tumor of urinary system in China.With the continuous improvement of living standards,bladder cancer incidence and mortality trends among our Chinses is rising.Finding a new technology to treat this disease is imperative.Small RNA molecules are now being recognized as master regulators of gene activity. Although known initially for their gene-silencing functions, recent discoveries have revealed that small RNAs can also activate gene expression.Some studies recently demonstrated that gene transcription can be stimulated by transfecting cells with small double-stranded RNA (dsRNA) constructs designed to target gene promoter sequences.Thus,these small activating RNAs (saRNAs) result in RNA-induced gene activation (RNAa). These studies established that the transcription of a number of genes is enhanced by saRNAs, including those encoding E-cadherin, p21,vascular endothelial growth factor (VEGF) and progesterone receptor(PR).For the past few years, researchers have been stalled by the challenge of delivering small RNA molecules in vivo due to its instability and nuclease easily degradation.The chemical modifications can protect the small double-stranded RNA against degradation by nucleases, minimize the off-target effects, increase the potency of the knockdown, and avoid the triggeri

英文关键词： ribose modification；saRNA；bladder cancer；；