Spliceosome mutations have become the most interesting mutations detected in human cancer in recent years. The spliceosome, a large, dynamic multimegadalton small nuclear ribonucleoprotein composed of small nuclear RNAs associated with proteins, is responsible for removing introns from precursor mRNA (premRNA) and generating mature, spliced mRNAs. SF3B1 is the largest subunit of the spliceosome factor 3b (SF3B) complex, which is a core component of spliceosomes. Recurrent somatic mutations in SF3B1 have been detected in human cancers, including hematological malignancies and solid tumors, and indicated to be related to patient prognosis. This review summarizes the research progress of SF3B1 mutations in cancer, including SF3B1 mutations in the HEAT domain, the multiple roles and aberrant splicing events of SF3B1 mutations in the pathogenesis of tumors, and changes in mutated cancer cells regarding sensitivity to SF3B small-molecule inhibitors. In addition, the potential of SF3B1 or its mutations to serve as biomarkers or therapeutic targets in cancer is discussed. The accumulated knowledge about SF3B1 mutations in cancer provides critical insight into the integral role the SF3B1 protein plays in mRNA splicing and suggests new targets for anticancer therapy.

中文翻译：

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SF3B1突变在癌症中的生物学功能和临床意义。

剪接体突变已成为近年来在人类癌症中检测到的最有趣的突变。剪接体是由与蛋白质相关的小核RNA组成的大型动态多兆小核核糖核蛋白，负责从前体mRNA（premRNA）去除内含子并产生成熟的剪接mRNA。SF3B1是剪接体因子3b（SF3B）复合体的最大亚基，它是剪接体的核心成分。在人类癌症中已检测到SF3B1的复发性体细胞突变，包括血液系统恶性肿瘤和实体瘤，并表明与患者的预后有关。这篇综述总结了癌症中SF3B1突变的研究进展，包括HEAT域中的SF3B1突变，SF3B1突变在肿瘤发病机制中的多重作用和异常剪接事件，以及突变细胞对SF3B小分子抑制剂敏感性的变化。另外，还讨论了SF3B1或其突变作为癌症中的生物标志物或治疗靶标的潜力。关于癌症中SF3B1突变的积累知识为SF3B1蛋白在mRNA剪接中发挥的不可或缺的作用提供了重要的见识，并提出了抗癌治疗的新目标。