Chen Si, Sun Heng, Miao Kai, Deng Chu-Xia
Faculty of Health Sciences, University of Macau, Macau SAR, China.
Int J Biol Sci. 2016 Nov 4;12(12):1427-1436. doi: 10.7150/ijbs.17421. eCollection 2016.
Cancer development is a multistep process triggered by innate and acquired mutations, which cause the functional abnormality and determine the initiation and progression of tumorigenesis. Gene editing is a widely used engineering tool for generating mutations that enhance tumorigenesis. The recent developed clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) system renews the genome editing approach into a more convenient and efficient way. By rapidly introducing genetic modifications in cell lines, organs and animals, CRISPR-Cas9 system extends the gene editing into whole genome screening, both in loss-of-function and gain-of-function manners. Meanwhile, the system accelerates the establishment of animal cancer models, promoting studies for cancer research. Furthermore, CRISPR-Cas9 system is modified into diverse innovative tools for observing the dynamic bioprocesses in cancer studies, such as image tracing for targeted DNA, regulation of transcription activation or repression. Here, we view recent technical advances in the application of CRISPR-Cas9 system in cancer genetics, large-scale cancer driver gene hunting, animal cancer modeling and functional studies.
癌症发展是一个由先天性和后天性突变引发的多步骤过程,这些突变会导致功能异常,并决定肿瘤发生的起始和进展。基因编辑是一种广泛应用的工程工具,用于产生增强肿瘤发生的突变。最近开发的成簇规律间隔短回文重复序列-CRISPR相关蛋白9(CRISPR-Cas9)系统将基因组编辑方法更新为一种更便捷高效的方式。通过在细胞系、器官和动物中快速引入基因修饰,CRISPR-Cas9系统将基因编辑扩展到全基因组筛选,包括功能丧失和功能获得两种方式。同时,该系统加速了动物癌症模型的建立,促进了癌症研究。此外,CRISPR-Cas9系统被改进为多种创新工具,用于观察癌症研究中的动态生物过程,如靶向DNA的图像追踪、转录激活或抑制的调控。在此,我们探讨CRISPR-Cas9系统在癌症遗传学、大规模癌症驱动基因搜寻、动物癌症建模和功能研究应用中的最新技术进展。