Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Aix Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM) UMR 7288, Parc Scientifique de Luminy, Marseille, France.
Semin Liver Dis. 2019 May;39(2):261-274. doi: 10.1055/s-0039-1678725. Epub 2019 Mar 25.
Hepatocellular carcinoma (HCC) is a devastating and prevalent cancer with limited treatment options. Technological advances have enabled genetic screens to be employed in HCC model systems to characterize genes regulating tumor initiation and growth. Relative to traditional methods for studying cancer biology, such as candidate gene approaches or expression analysis, genetic screens have several advantages: they are unbiased, with no selection; can directly annotate gene function; and can uncover gene-gene interactions. In HCC, three main types of screens have been conducted and are reviewed here: (1) transposon-based mutagenesis screens, (2) knockdown screens using RNA interference (RNAi) or the CRISPR/Cas9 system, and (3) overexpression screens using CRISPR activation (CRISPRa) or cDNAs. These methods will be valuable in future genetic screens to delineate the mechanisms underlying drug resistance and to identify new treatments for HCC.
肝细胞癌 (HCC) 是一种具有破坏性且普遍存在的癌症，治疗选择有限。技术进步使基因筛选能够应用于 HCC 模型系统，以表征调节肿瘤发生和生长的基因。与研究癌症生物学的传统方法（如候选基因方法或表达分析）相比，基因筛选具有几个优势：它们是无偏见的，没有选择；可以直接注释基因功能；并且可以发现基因-基因相互作用。在 HCC 中，已经进行了三种主要类型的筛选，本文对此进行了综述：（1）转座子诱变筛选，（2）使用 RNA 干扰 (RNAi) 或 CRISPR/Cas9 系统的敲低筛选，以及（3）使用 CRISPR 激活 (CRISPRa) 或 cDNA 的过表达筛选。这些方法将在未来的遗传筛选中具有重要价值，以阐明耐药性的机制，并为 HCC 确定新的治疗方法。
