Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Trends Cancer. 2020 Aug;6(8):631-644. doi: 10.1016/j.trecan.2020.04.011. Epub 2020 May 17.
RNA splicing is an essential process that governs many aspects of cellular proliferation, survival, and differentiation. Considering the importance of RNA splicing in gene regulation, alterations in this pathway have been implicated in many human cancers. Large-scale genomic studies have uncovered a spectrum of splicing machinery mutations that contribute to tumorigenesis. Moreover, cancer cells are capable of hijacking the expression of RNA-binding proteins (RBPs), leading to dysfunctional gene splicing and tumor-specific dependencies. Advances in next-generation RNA sequencing have revealed tumor-specific isoforms associated with these alterations, including the presence of neoantigens, which serve as potential immunotherapeutic targets. In this review, we discuss the various mechanisms by which cancer cells exploit RNA splicing to promote tumor growth and the current therapeutic landscape for splicing-based therapies.
RNA 剪接是一种重要的过程，它控制着细胞增殖、存活和分化的许多方面。鉴于 RNA 剪接在基因调控中的重要性，该途径的改变与许多人类癌症有关。大规模的基因组研究揭示了一系列剪接机制突变，这些突变有助于肿瘤发生。此外，癌细胞能够劫持 RNA 结合蛋白 (RBP) 的表达，导致功能失调的基因剪接和肿瘤特异性依赖性。新一代 RNA 测序技术的进步揭示了与这些改变相关的肿瘤特异性异构体，包括新抗原的存在，它们可作为潜在的免疫治疗靶点。在这篇综述中，我们讨论了癌细胞利用 RNA 剪接促进肿瘤生长的各种机制，以及基于剪接的治疗方法的当前治疗现状。
