剪接激酶介导肿瘤细胞内mRNA可变剪接失调:机遇与挑战  

Dysregulation of mRNA alternative splicing guided by splicing kinases in cancer cells:opportunities and challenges

作　　者：安文哲 李雪冰[2] 周雪霞 AN Wenzhe;LI Xuebing;ZHOU Xuexia(Tianjin Key Laboratory of Injuries,Variations and Regeneration of the Nervous System,Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System of Education Ministry,Tianjin Neurological Institute,Tianjin Medical University General Hospital,Tianjin 300052,China;Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment,Department of Lung Cancer Surgery,Tianjin Lung Cancer Institute,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院,天津市神经病学研究所,天津市神经损伤变异与再生重点实验室,教育部中枢创伤修复与再生重点实验室,天津300052 [2]天津医科大学总医院,天津市肺癌研究所肺部肿瘤外科,天津市肺癌转移与肿瘤微环境重点实验室,天津300052

出　　处：《生命的化学》2022年第11期2079-2088,共10页Chemistry of Life

基　　金：国家自然科学基金项目(81972354,82172901,82273019);天津市自然科学基金多元投入基金项目青年项目(21JCQNJC01440);天津市自然科学基金项目(18JCYBJC92100);中国抗癌协会基金项目(CFC2020kyxm003);天津市医学重点学科(专科)建设项目(TJYXZDXK-061B);天津市肺癌研究所面上项目(TJLCMS2021-03)。

摘　　要：可变剪接是前体mRNA加工过程中的一个关键步骤,其主要作用是确保基因的精确表达以及人类转录组的多样性。剪接调控网络的失常可导致多种疾病发生并促进肿瘤发生发展。调控可变剪接的剪接因子可受到多种激酶(即剪接激酶)的磷酸化修饰,这些剪接激酶主要包括SR蛋白激酶(SR-protein kinases,SRPKs)和CDC2样激酶(CDC2-like kinases,CLKs)。经磷酸化修饰后,剪接因子可能会改变自身的亚细胞定位及其自身与靶标转录本、蛋白因子之间的相互作用,从而对剪接反应的最终结果输出产生重要影响。本综述主要总结了剪接激酶在肿瘤中的现有研究进展,并讨论了以剪接激酶为靶标的肿瘤新治疗途径面临的机遇与挑战。Alternative splicing represents a vital step in pre-mRNA processing,which ensure precise gene expression and diversification of human transcriptome.Disruptions to splicing regulatory network underlie a host of human diseases and contribute to cancer development and progression.Splicing factors that control alternative splicing are phosphorylated by multiple kinases(named splicing kinases),which mainly include SR-protein kinases(SRPKs) and CDC2-like kinases(CLKs).Phosphorylation of splicing factors might alter their subcellular localization and interactions with target transcripts and proteins,thus significantly contributing to the final outcome of splicing reactions.In this review we aim to summarize the current knowledge on the roles of splicing kinases in cancer,and discuss opportunities and challenges of developing novel therapeutic approaches targeting splicing kinases.

关 键 词：剪接激酶 SR蛋白激酶 CDC2样激酶 肿瘤 

分 类 号：R730.2[医药卫生—肿瘤]