Division of Gene Therapy Science, Department of Genome Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Cells. 2021 Apr 16;10(4):923. doi: 10.3390/cells10040923.
RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5' and 3' splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.
RNA 剪接是前体 mRNA（pre-mRNA）成熟过程中的一个关键步骤，通过去除内含子和外显子来实现。pre-mRNA 中外显子和内含子的包含和排除的组合可以从有限数量的基因中产生大量成熟 mRNA 的多样性。癌细胞通过异常剪接调控获得治疗抵抗性和促进恶性肿瘤的发生，从而获得癌症特异性机制。剪接调控涉及许多因素，如蛋白质、非编码 RNA 和 DNA 序列，在多个步骤中起作用。因此，剪接的失调是由许多因素引起的，包括 RNA 剪接因子的突变、RNA 剪接因子的异常表达水平、小核核糖核蛋白的生物发生、snRNA 的突变或参与剪接调控的基因组序列，如 5'和 3'剪接位点、分支点、剪接增强子/沉默子，以及影响剪接谱的染色质状态的变化。本文综述了与癌症相关的 RNA 剪接失调及其相关的治疗方法。
