Silipo Marco, Gautrey Hannah, Tyson-Capper Alison
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
J Mol Cell Biol. 2015 Oct;7(5):388-401. doi: 10.1093/jmcb/mjv027. Epub 2015 May 5.
It is well known that many genes implicated in the development and progression of breast cancer undergo aberrant alternative splicing events to produce proteins with pro-cancer properties. These changes in alternative splicing can arise from mutations or single-nucleotide polymorphisms (SNPs) within the DNA sequences of cancer-related genes, which can strongly affect the activity of splicing factors and influence the splice site choice. However, it is important to note that absence of mutations is not sufficient to prevent misleading choices in splice site selection. There is now increasing evidence to demonstrate that the expression profile of ten splicing factors (including SRs and hnRNPs) and eight RNA-binding proteins changes in breast cancer cells compared with normal cells. These modifications strongly influence the alternative splicing pattern of many cancer-related genes despite the absence of any detrimental mutations within their DNA sequences. Thus, a comprehensive assessment of the splicing factor status in breast cancer is important to provide insights into the mechanisms that lead to breast cancer development and metastasis. Whilst most studies focus on mutations that affect alternative splicing in cancer-related genes, this review focuses on splicing factors and RNA-binding proteins that are themselves deregulated in breast cancer and implicated in cancer-related alternative splicing events.
众所周知，许多与乳腺癌发生和发展相关的基因会发生异常可变剪接事件，从而产生具有促癌特性的蛋白质。可变剪接的这些变化可能源于癌症相关基因DNA序列中的突变或单核苷酸多态性（SNP），这会强烈影响剪接因子的活性并影响剪接位点的选择。然而，需要注意的是，没有突变并不足以防止在剪接位点选择上出现错误选择。现在有越来越多的证据表明，与正常细胞相比，乳腺癌细胞中十种剪接因子（包括SR蛋白和hnRNP蛋白）和八种RNA结合蛋白的表达谱发生了变化。尽管这些癌症相关基因的DNA序列中没有任何有害突变，但这些修饰强烈影响了许多癌症相关基因的可变剪接模式。因此，全面评估乳腺癌中的剪接因子状态对于深入了解导致乳腺癌发生和转移的机制非常重要。虽然大多数研究关注影响癌症相关基因可变剪接的突变，但本综述关注的是在乳腺癌中自身失调并与癌症相关可变剪接事件有关的剪接因子和RNA结合蛋白。
