Culjkovic-Kraljacic Biljana, Borden Katherine L B
Institute for Research in Immunology and Cancer, Department of Pathology and Cell Biology, University of Montreal, Montreal, QC, Canada.
Front Genet. 2018 Nov 5;9:512. doi: 10.3389/fgene.2018.00512. eCollection 2018.
Traditionally, cancer is viewed as a disease driven by genetic mutations and/or epigenetic and transcriptional dysregulation. While these are undoubtedly important drivers, many recent studies highlight the disconnect between the proteome and the genome or transcriptome. At least in part, this disconnect arises as a result of dysregulated RNA metabolism which underpins the altered proteomic landscape observed. Thus, it is important to understand the basic mechanisms governing post-transcriptional control and how these processes can be co-opted to drive cancer cell phenotypes. In some cases, groups of mRNAs that encode protein involved in specific oncogenic processes can be co-regulated at multiple processing levels in order to turn on entire biochemical pathways. Indeed, the RNA regulon model was postulated as a means to understand how cells coordinately regulate transcripts encoding proteins in the same biochemical pathways. In this review, we describe some of the basic mRNA processes that are dysregulated in cancer and the biological impact this has on the cell. This dysregulation can affect networks of RNAs simultaneously thereby underpinning the oncogenic phenotypes observed.
传统上,癌症被视为一种由基因突变和/或表观遗传及转录失调驱动的疾病。虽然这些无疑是重要的驱动因素,但最近许多研究强调了蛋白质组与基因组或转录组之间的脱节。这种脱节至少部分是由于RNA代谢失调导致的,而RNA代谢失调是观察到的蛋白质组景观改变的基础。因此,了解转录后调控的基本机制以及这些过程如何被用于驱动癌细胞表型非常重要。在某些情况下,编码参与特定致癌过程的蛋白质的mRNA群体可以在多个加工水平上被共同调控,从而开启整个生化途径。事实上,RNA调节子模型被提出作为一种理解细胞如何协调调控同一生化途径中编码蛋白质的转录本的方法。在这篇综述中,我们描述了一些在癌症中失调的基本mRNA过程以及这对细胞产生的生物学影响。这种失调可以同时影响RNA网络,从而支撑所观察到的致癌表型。