Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom of Great Britain and Northern Ireland.
Cellular Pathology Department, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, United Kingdom of Great Britain and Northern Ireland.
Biochim Biophys Acta Gene Regul Mech. 2019 Nov-Dec;1862(11-12):194388. doi: 10.1016/j.bbagrm.2019.05.006. Epub 2019 May 29.
Lung cancer has the highest mortality rate of all cancers worldwide. Lung cancer is a very heterogeneous disease that is often diagnosed at later stages which have a poor prognosis. Aberrant alternative splicing patterns found in lung cancer contribute to important cell functions. These include changes in splicing for the BCL2L1, MDM2, MDM4, NUMB and MET genes during lung tumourigenesis, to affect pathways involved in apoptosis, cell proliferation and cellular cohesion. Global analyses of RNASeq datasets suggest there may be many more potentially influential aberrant splicing events that need to be investigated in lung cancer. Changes in expression of the splicing factors that regulate alternative splicing events have also been identified in lung cancer. Of these, changes in expression of QKI, RBM4, RBM5, RBM6, RBM10 and SRSF1 proteins regulate many of the most frequently referenced aberrant splicing events in lung cancer. The expanding list of genes known to be aberrantly spliced in lung cancer along with the altered expression of splicing factors that regulate them are providing new clues as to how lung cancer develops, and how these events can be exploited for better treatment. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.
肺癌是全球癌症死亡率最高的癌症。肺癌是一种非常异质的疾病，通常在晚期诊断，预后较差。在肺癌中发现的异常选择性剪接模式有助于重要的细胞功能。这些包括在肺肿瘤发生过程中 BCL2L1、MDM2、MDM4、NUMB 和 MET 基因的剪接变化，以影响涉及细胞凋亡、细胞增殖和细胞黏附的途径。对 RNASeq 数据集的全球分析表明，可能还有许多更具潜在影响的异常剪接事件需要在肺癌中进行研究。在肺癌中也已经鉴定出调节选择性剪接事件的剪接因子表达的变化。其中，QKI、RBM4、RBM5、RBM6、RBM10 和 SRSF1 蛋白表达的变化调节了肺癌中许多最常被引用的异常剪接事件。已知在肺癌中异常剪接的基因不断增加，以及调节它们的剪接因子的表达改变，为肺癌的发展以及如何利用这些事件进行更好的治疗提供了新的线索。本文是一个题为“RNA 结构和剪接调控”的特刊的一部分，由 Francisco Baralle、Ravindra Singh 和 Stefan Stamm 编辑。
