Lv Xuemei, Sun Xiaoyu, Gao Yang, Song Xinyue, Hu Xiaoyun, Gong Lang, Han Li, He Miao, Wei Minjie
Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, P. R. China.
Central Laboratory, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China.
J Exp Clin Cancer Res. 2025 Jan 30;44(1):32. doi: 10.1186/s13046-025-03279-w.
The excision of introns from pre-mRNA is a crucial process in the expression of the majority of genes. Alternative splicing allows a single gene to generate diverse mRNA and protein products. Aberrant RNA splicing is recognized as a molecular characteristic present in almost all types of tumors. Therefore, identifying cancer-specific subtypes from aberrant processing offers new opportunities for therapeutic development. Numerous splicing modulators, each utilizing different mechanisms, have been developed as promising anticancer therapies, some of which are in clinical trials. In this review, we summarize the splice-altered signatures of cancer cell transcriptomes and the contributions of splicing aberrations to tumorigenesis and progression. Especially, we discuss current and emerging RNA splicing-targeted strategies for cancer therapy, including pharmacological approaches and splice-switching antisense oligonucleotides (ASOs). Finally, we address the challenges and opportunities in translating these findings into clinical practice.
从前体mRNA中切除内含子是大多数基因表达过程中的一个关键步骤。可变剪接使单个基因能够产生多种mRNA和蛋白质产物。异常RNA剪接被认为是几乎所有类型肿瘤中都存在的一种分子特征。因此，从异常加工过程中识别癌症特异性亚型为治疗发展提供了新的机会。许多剪接调节剂，每种都利用不同的机制，已被开发为有前景的抗癌疗法，其中一些正在进行临床试验。在这篇综述中，我们总结了癌细胞转录组的剪接改变特征以及剪接异常对肿瘤发生和进展的影响。特别是，我们讨论了当前和新兴的针对癌症治疗的RNA剪接靶向策略，包括药理学方法和剪接转换反义寡核苷酸（ASO）。最后，我们阐述了将这些发现转化为临床实践中的挑战和机遇。
