Aberrant RNA Splicing in Cancer
Aberrant RNA Splicing in Cancer
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DOI：
10.1146/annurev-cancerbio-030617-050407
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Abdel-Wahab, Omar
中科院分区：
文献类型：
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作者：
Escobar-Hoyos, Luisa;Knorr, Katherine;Abdel-Wahab, Omar
RNA 剪接是去除成熟 RNA 片段以产生成熟 RNA 的酶促过程，是蛋白质组多样性和基因表达调节剂的关键介质。对癌症基因组和转录组的系统测序的增加已经确定了相对于正常细胞而言，癌症中 RNA 剪接发生改变的多种方式。这些发现与多种癌症中剪接因子中反复发生的功能改变突变的发现相结合，表明剪接的改变是肿瘤发生的驱动因素。对癌症中剪接改变的更深入的表征与药理学干扰剪接的努力以及破坏癌症患者剪接的小分子的早期临床开发相平行。在这里，我们回顾了癌症剪接的全球变化、对癌症转化至关重要的有丝分裂途径的剪接调节以及针对癌症剪接进行治疗的努力的最新研究。
RNA splicing, the enzymatic process of removing segments of premature RNA to produce mature RNA, is a key mediator of proteome diversity and regulator of gene expression. Increased systematic sequencing of the genome and transcriptome of cancers has identified a variety of means by which RNA splicing is altered in cancer relative to normal cells. These findings, in combination with the discovery of recurrent change-of-function mutations in splicing factors in a variety of cancers, suggest that alterations in splicing are drivers of tumorigenesis. Greater characterization of altered splicing in cancer parallels increasing efforts to pharmacologically perturb splicing and early-phase clinical development of small molecules that disrupt splicing in patients with cancer. Here we review recent studies of global changes in splicing in cancer, splicing regulation of mitogenic pathways critical in cancer transformation, and efforts to therapeutically target splicing in cancer.