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mRNA 剪接机制的生物学及其在癌症中的失调为治疗提供了机会。

Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.

机构信息

Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

出版信息

Int J Mol Sci. 2021 May 12;22(10):5110. doi: 10.3390/ijms22105110.

DOI:10.3390/ijms22105110
PMID:34065983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8150589/
Abstract

Dysregulation of messenger RNA (mRNA) processing-in particular mRNA splicing-is a hallmark of cancer. Compared to normal cells, cancer cells frequently present aberrant mRNA splicing, which promotes cancer progression and treatment resistance. This hallmark provides opportunities for developing new targeted cancer treatments. Splicing of precursor mRNA into mature mRNA is executed by a dynamic complex of proteins and small RNAs called the spliceosome. Spliceosomes are part of the supraspliceosome, a macromolecular structure where all co-transcriptional mRNA processing activities in the cell nucleus are coordinated. Here we review the biology of the mRNA splicing machinery in the context of other mRNA processing activities in the supraspliceosome and present current knowledge of its dysregulation in lung cancer. In addition, we review investigations to discover therapeutic targets in the spliceosome and give an overview of inhibitors and modulators of the mRNA splicing process identified so far. Together, this provides insight into the value of targeting the spliceosome as a possible new treatment for lung cancer.

摘要

mRNA 处理（尤其是 mRNA 剪接）的失调是癌症的一个标志。与正常细胞相比，癌细胞经常表现出异常的 mRNA 剪接，这促进了癌症的进展和治疗耐药性。这个标志为开发新的靶向癌症治疗提供了机会。前体 mRNA 剪接成熟 mRNA 是由称为剪接体的蛋白质和小 RNA 动态复合物执行的。剪接体是超剪接体的一部分，超剪接体是一种大分子结构，其中细胞核中所有共转录的 mRNA 加工活性都得到协调。在这里，我们在超剪接体中其他 mRNA 加工活性的背景下综述了 mRNA 剪接机制的生物学，并介绍了其在肺癌中失调的最新知识。此外，我们还综述了发现剪接体治疗靶点的研究，并概述了迄今为止发现的 mRNA 剪接过程的抑制剂和调节剂。总之，这深入了解了将剪接体作为治疗肺癌的一种新方法的潜在价值。

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