乙酰化赖氨酸基因线路靶向治疗膀胱癌的分子机制研究

The current methods of diagnosis and treatment of bladder cancer cannot effectively distinguish between normal cells and bladder cancer cells by a single target, which is in need of more specific precision medical technology research for bladder cancer targeting therapy. Several efficient bladder cancer targets were found in our bladder cancer systems biology and genomics research, including human telomerase reverse transcriptase (hTERT) promotor. Compared to the wild type hTERT promoter, the mutant hTERT promoters had higher transcription efficiency and maintained bladder cancer specificity. We suggest that targeting multiple targets at the same time could improve the bladder cancer recognition specificity in treatment. The project is armed to identify new bladder cancer-specific promoters, regulate genes related to bladder cancer cell migration, invasion and proliferation, engineer genetic circuits for manipulation of live cells , distinguish between normal cells and bladder cancer cells by means of logic AND gate. Our research would reveal the molecular mechanism of genetic circuits in bladder cancer and provide theoretical and experimental basis for the development of new bladder cancer treatment methods.

目前膀胱癌诊治还不能有效地通过单个靶点区分正常细胞和膀胱癌细胞，急需研发对膀胱癌更加特异的精准医疗技术，提高膀胱癌治疗的靶向性。本项目前期通过对膀胱癌系统生物学和基因组学研究，鉴定出多个膀胱癌特异的有效靶点，包括人端粒酶逆转录酶基因hTERT启动子，进而发现其人工突变型hTERT启动子比野生型hTERT启动子具有更高的启动效率，而且保持了启动子原有的肿瘤特异性。我们推测：同时靶向包括hTERT启动子在内的多个靶点可提高膀胱癌治疗的肿瘤识别特异性。本项目拟：1、分析改造膀胱癌特异启动子；2、调控干预膀胱癌迁移、侵袭和增殖的效应基因，构建监控活细胞状态变化的基因线路；3、通过逻辑与门的方式多靶点区分正常细胞和膀胱癌细胞，并揭示基因线路干预膀胱癌的分子机制。上述研究结果将为开发膀胱癌的精准治疗方法提供实验基础与理论依据。

目前的膀胱癌诊治方法不能有效地通过单个靶点区分正常细胞和膀胱癌细胞，急需研发对膀胱癌更加特异的精准医疗技术，提高膀胱癌治疗的靶向性。研究团队前期通过对膀胱癌系统生物学和基因组学的研究，鉴定出多个膀胱癌特异的有效靶点，但单个靶点的膀胱癌特异性并不够高，因此推测同时靶向膀胱癌的多个靶点能够提高膀胱癌治疗的肿瘤识别特异性。本项目旨在分析改造膀胱癌特异启动子，调控干预膀胱癌迁移、侵袭和增殖的效应基因，构建监控活细胞状态变化的基因线路，通过逻辑“与”门的方式多靶点区分正常细胞和膀胱癌细胞，并揭示基因线路干预膀胱癌的分子机制，为开发膀胱癌的精准治疗方法提供理论和实验依据。