基因组绝大多数转录产物为非编码RNA，阐明其作用已成为重要研究方向。本课题组前期研究证实：miR-101作用下调与膀胱癌进展密切相关，可作为研究膀胱癌发展机制及治疗策略的重要靶点，其内在调控机理有待进一步阐明。最新研究揭示了非编码RNA研究的全新领域：环状RNA（circRNA）作为一类细胞内稳定高表达、具有组织特异性的新型非编码RNA，可以以内源性竞争性RNA的形式抑制miRNA。生物信息学分析提示，RAN结合蛋白9编码区转录过程中能够产生两种circRNA，均具有miR-101的结合位点，且表达具有膀胱癌特异性。我们初步研究亦表明，膀胱癌中这两种circRNA表达均显著升高，过表达靶向circRNA能够进一步下调miR-101表达。本课题拟在此基础上，系统解析膀胱癌中miR-101与其靶向circRNA相互调控机制，并构建膀胱癌细胞特异性核酸转染体系，有望为膀胱癌的靶向治疗提供新策略。

It is now being realized that non-coding RNAs represent most of the human transcriptome, and functionalizing the non-coding space will undoubtedly lead to important insight about basic physiology and disease progression. Our previous study has confirmed that, the down-regulation of miR-101 is closely associated with the development of bladder cancer, and could be used as a target for exploring novel treatment strategies. The exact mechanism involved in the down-regulation of miR-101 in bladder cancer has still to be fully discovered. Evidence from computational analyses of expression data in Archaea and Mammalia suggests that the highly stable expressed endogenous circular RNAs (circRNAs) are more prevalent than previously thought. Recently, the tissue-specific circRNAs have been reported to act as an effective miRNA sponge and affect miRNA target gene activity. Bioinformatic analysis shows that two bladder cancer-specific circRNAs could be transcribed from the coding region of RNA-binding protein 9, and both of them have miR-101 binding sites. We also found that the two bladder cancer-specific cicrRNAs were obviously up-regulated in bladder cancer tissues, and over-expression of this circRNA could further suppress the expression of miR-101. In the project, we will systematically identify the regulation between miR-101 and its targeted cicrRNAs, and create the bladder cancer cell-targeted fusion protein of single-chain antibody against Uroplakin Ib and low molecular weight protamine to transport siRNA and shRNA. This work will build a solid theoretical foundation for functionalizing circRNAs, and develop a more selective strategy for targeted therapy in bladder cancer.