Department of Biological Sciences, College of Science and Health, Benedictine University, Lisle, IL 60532, USA.
Biomolecules. 2023 Mar 20;13(3):561. doi: 10.3390/biom13030561.
Cancer is among the leading causes of mortality worldwide. While considerable attention has been given to genetic and epigenetic sources of cancer-specific cellular activities, the role of alternative mRNA splicing has only recently received attention as a major contributor to cancer initiation and progression. The distribution of alternate mRNA splicing variants in cancer cells is different from their non-cancer counterparts, and cancer cells are more sensitive than non-cancer cells to drugs that target components of the splicing regulatory network. While many of the alternatively spliced mRNAs in cancer cells may represent "noise" from splicing dysregulation, certain recurring splicing variants have been shown to contribute to tumor progression. Some pathogenic splicing disruption events result from mutations in cis-acting splicing regulatory sequences in disease-associated genes, while others may result from shifts in balance among naturally occurring alternate splicing variants among mRNAs that participate in cell cycle progression and the regulation of apoptosis. This review provides examples of cancer-related alternate splicing events resulting from each step of mRNA processing and the promising therapies that may be used to address them.
癌症是全球主要的死亡原因之一。尽管人们已经关注了癌症特异性细胞活动的遗传和表观遗传来源，但作为癌症发生和发展的主要因素之一，选择性剪接 mRNA 的作用直到最近才受到关注。癌细胞中选择性剪接 mRNA 变体的分布与其非癌细胞不同，并且癌细胞比非癌细胞对靶向剪接调控网络成分的药物更敏感。虽然癌细胞中的许多选择性剪接 mRNA 可能代表剪接失调的“噪声”，但某些反复出现的剪接变体已被证明有助于肿瘤进展。一些致病的剪接破坏事件是由疾病相关基因中顺式作用剪接调控序列的突变引起的，而其他事件可能是由于参与细胞周期进程和细胞凋亡调控的 mRNA 中天然存在的选择性剪接变体之间的平衡发生变化引起的。本综述提供了由 mRNA 加工的每个步骤引起的与癌症相关的选择性剪接事件的例子，以及可能用于解决这些问题的有前途的治疗方法。
