The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, South Baixiang, Ouhai District, Wenzhou, 325015, Zhejiang, People's Republic of China.
Department of Food Microbiology, Faculty of Science, University of Copenhagen, 1958, Frederiksberg C. Copenhagen, Denmark.
J Cancer Res Clin Oncol. 2023 Sep;149(12):9557-9575. doi: 10.1007/s00432-023-04747-6. Epub 2023 May 24.
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas technology is a molecular tool specific to sequences for engineering genomes. Among diverse clusters of Cas proteins, the class 2/type II CRISPR/Cas9 system, despite several challenges, such as off-target effects, editing efficiency, and efficient delivery, has shown great promise for driver gene mutation discovery, high-throughput gene screening, epigenetic modulation, nucleic acid detection, disease modeling, and more importantly for therapeutic purposes. CRISPR-based clinical and experimental methods have applications across a wide range of areas, especially for cancer research and, possibly, anticancer therapy. On the other hand, given the influential role of microRNAs (miRNAs) in the regulations of cellular division, carcinogenicity, tumorigenesis, migration/invasion, and angiogenesis in diverse normal and pathogenic cellular processes, in different stages of cancer, miRNAs are either oncogenes or tumor suppressors, according to what type of cancer they are involved in. Hence, these noncoding RNA molecules are conceivable biomarkers for diagnosis and therapeutic targets. Moreover, they are suggested to be adequate predictors for cancer prediction. Conclusive evidence proves that CRISPR/Cas system can be applied to target small non-coding RNAs. However, the majority of studies have highlighted the application of the CRISPR/Cas system for targeting protein-coding regions. In this review, we specifically discuss diverse applications of CRISPR-based tools for probing miRNA gene function and miRNA-based therapeutic involvement in different types of cancers.
簇状规律间隔短回文重复 (CRISPR)/Cas 技术是一种专门针对基因组工程序列的分子工具。在不同的 Cas 蛋白簇中，尽管存在脱靶效应、编辑效率和有效传递等诸多挑战，但 2 类/II 型 CRISPR/Cas9 系统在发现驱动基因突变、高通量基因筛选、表观遗传调节、核酸检测、疾病建模等方面具有很大的应用前景，更重要的是，在治疗方面具有很大的应用前景。基于 CRISPR 的临床和实验方法在广泛的领域都有应用，特别是在癌症研究方面，并且可能在抗癌治疗方面也有应用。另一方面，鉴于 microRNAs (miRNAs) 在细胞分裂、致癌性、肿瘤发生、迁移/侵袭和血管生成等多种正常和病理细胞过程中的调控作用，miRNAs 在不同类型的癌症中要么是癌基因，要么是肿瘤抑制基因，这取决于它们所涉及的癌症类型。因此，这些非编码 RNA 分子可以作为诊断和治疗靶点的生物标志物。此外，它们被认为是癌症预测的合适预测因子。确凿的证据证明，CRISPR/Cas 系统可用于靶向小非编码 RNA。然而，大多数研究都强调了 CRISPR/Cas 系统在靶向蛋白编码区中的应用。在这篇综述中，我们专门讨论了基于 CRISPR 的工具在探测 miRNA 基因功能和 miRNA 治疗方面在不同类型癌症中的应用。
