启动子状态对RNA激活效力的影响以及前列腺癌中激活RNA筛选策略的优化

前列腺癌是全世界男性面临的重要的健康问题。前列腺癌，尤其是去势抵抗性前列腺癌的治疗仍然面临挑战。靶向基因启动子区的小RNA能够诱导靶基因的转录激活，为基因的功能研究和肿瘤的靶向治疗提供了全新的策略。传统小激活RNA的设计筛选成功率较低，阻碍了RNA激活研究的开展。近年来研究提示，小激活RNA对靶基因的激活效力可能受到启动子区转录产物、DNA甲基化水平以及组蛋白修饰水平等因素的影响。本研究通过组学的研究方法，系统研究RNA激活效力与基因启动子区状态之间的关联，探索并验证有利于RNA激活的基因启动子状态，优化小激活RNA的设计筛选策略，最终筛选出能够转化应用于临床前列腺癌治疗的小激活RNA。

Prostate cancer becomes one of the most critical health issue in the world male population. The treatment of prostate caner,especially the castration resistant prostate cancer, remains challenging. Small RNAs, which target the promoter region of genes, may have the ability to activate the gene expression on the transcriptional level. Application of this kind of small RNAs becomes a notable strategy for gene function research and tumor targeted therapy. However, it is still inefficient to obtain small activating RNAs by triditional design and screaning method, which impedes the further research of RNA activation. Rescent studies indicated that several issues, such as transcripts from promoter regions, DNA methylation and histone modifications, may affect the efficacy of small RNA induced gene activation. In this study, the relationship between RNA activation efficacy and the variable promoter status is fully researched by epigenomic methods in order to identify the appropriate promoter status for RNA activation and to improve the screaning strategy for small activating RNA. The effective (or functional) small RNAs are also tested for their abilities of translational application into prostate cancer therapy.