Lucere Kathleen M, O'Malley Megan M R, Diermeier Sarah D
Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand.
Cancers (Basel). 2020 Dec 9;12(12):3695. doi: 10.3390/cancers12123695.
Recent technological advancements such as CRISPR/Cas-based systems enable multiplexed, high-throughput screening for new therapeutic targets in cancer. While numerous functional screens have been performed on protein-coding genes to date, long non-coding RNAs (lncRNAs) represent an emerging class of potential oncogenes and tumor suppressors, with only a handful of large-scale screens performed thus far. Here, we review in detail currently available screening approaches to identify new lncRNA drivers of tumorigenesis and tumor progression. We discuss the various approaches of genomic and transcriptional targeting using CRISPR/Cas9, as well as methods to post-transcriptionally target lncRNAs via RNA interference (RNAi), antisense oligonucleotides (ASOs) and CRISPR/Cas13. We discuss potential advantages, caveats and future applications of each method to provide an overview and guide on investigating lncRNAs as new therapeutic targets in cancer.
近期诸如基于CRISPR/Cas的系统等技术进步,使得对癌症中新的治疗靶点进行多重、高通量筛选成为可能。尽管迄今为止已经对蛋白质编码基因进行了大量功能筛选,但长链非编码RNA(lncRNA)代表了一类新兴的潜在癌基因和肿瘤抑制因子,到目前为止仅进行了少数大规模筛选。在这里,我们详细综述了目前可用于鉴定肿瘤发生和肿瘤进展新lncRNA驱动因子的筛选方法。我们讨论了使用CRISPR/Cas9进行基因组和转录靶向的各种方法,以及通过RNA干扰(RNAi)、反义寡核苷酸(ASO)和CRISPR/Cas13对lncRNA进行转录后靶向的方法。我们讨论了每种方法的潜在优势、注意事项和未来应用,以提供关于将lncRNA作为癌症新治疗靶点进行研究的概述和指南。