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癌症中SF3B1突变的生物学功能及临床意义

The biological function and clinical significance of SF3B1 mutations in cancer.

作者信息

Zhou Zhixia, Gong Qi, Wang Yin, Li Mengkun, Wang Lu, Ding Hongfei, Li Peifeng

机构信息

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266012 People's Republic of China.

The Second Clinical Medical College of Qingdao University, Qingdao, 266042 People's Republic of China.

出版信息

Biomark Res. 2020 Sep 3;8:38. doi: 10.1186/s40364-020-00220-5. eCollection 2020.

DOI:10.1186/s40364-020-00220-5
PMID:32905346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7469106/
Abstract

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 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 mutations in cancer, including mutations in the HEAT domain, the multiple roles and aberrant splicing events of mutations in the pathogenesis of tumors, and changes in mutated cancer cells regarding sensitivity to SF3B small-molecule inhibitors. In addition, the potential of or its mutations to serve as biomarkers or therapeutic targets in cancer is discussed. The accumulated knowledge about mutations in cancer provides critical insight into the integral role the SF3B1 protein plays in mRNA splicing and suggests new targets for anticancer therapy.

摘要

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。剪接体是一种由与蛋白质相关的小核RNA组成的大型动态多兆道尔顿小核核糖核蛋白，负责从前体mRNA（pre-mRNA）中去除内含子并生成成熟的剪接mRNA。SF3B1是剪接体因子3b（SF3B）复合体的最大亚基，而SF3B复合体是剪接体的核心组成部分。在包括血液系统恶性肿瘤和实体瘤在内的人类癌症中已检测到SF3B1的复发性体细胞突变，并且表明这些突变与患者预后相关。本综述总结了癌症中SF3B1突变的研究进展，包括HEAT结构域中的SF3B1突变、SF3B1突变在肿瘤发病机制中的多种作用和异常剪接事件，以及突变癌细胞对SF3B小分子抑制剂敏感性的变化。此外，还讨论了SF3B1或其突变作为癌症生物标志物或治疗靶点的潜力。关于癌症中SF3B1突变积累的知识为深入了解SF3B1蛋白在mRNA剪接中所起的整体作用提供了关键见解，并为抗癌治疗提出了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/4c0e1063445d/40364_2020_220_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/148334997990/40364_2020_220_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/4c0e1063445d/40364_2020_220_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/148334997990/40364_2020_220_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/350e0af2c2be/40364_2020_220_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/6fe095961534/40364_2020_220_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/984a07e8f2cc/40364_2020_220_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3da/7469106/4c0e1063445d/40364_2020_220_Fig5_HTML.jpg

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