Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Exp Med. 2024 Nov 4;221(11). doi: 10.1084/jem.20230891. Epub 2024 Sep 24.
Dysregulation of the flow of information from genomic DNA to RNA to protein occurs within all cancer types. In this review, we described the current state of understanding of how RNA processing is dysregulated in cancer with a focus on mutations in the RNA splicing factor machinery that are highly prevalent in hematologic malignancies. We discuss the downstream effects of these mutations highlighting both individual genes as well as common pathways that they perturb. We highlight examples of how alterations in RNA processing have been harnessed for therapeutic intent as well as to promote the selective toxicity of cancer cells.
所有癌症类型中都存在从基因组 DNA 到 RNA 再到蛋白质的信息流失调。在这篇综述中,我们描述了目前对癌症中 RNA 加工失调的理解状态,重点介绍了在血液恶性肿瘤中高度普遍存在的 RNA 剪接因子机制中的突变。我们讨论了这些突变的下游效应,突出了它们扰乱的单个基因和常见途径。我们还举例说明了如何利用 RNA 加工的改变来达到治疗目的,并促进癌细胞的选择性毒性。