López-Urrutia Eduardo, Campos-Parra Alma, Herrera Luis Alonso, Pérez-Plasencia Carlos
Genomics Laboratory, UBIMED, Faculty of Higher Studies-Iztacala, National Autonomous University, Tlalnepantla, 54090 State of Mexico, Mexico.
Genomics Laboratory, National Cancer Institute of Mexico, Tlalpan, 14680 Mexico City, Mexico.
Oncol Lett. 2017 Nov;14(5):5114-5120. doi: 10.3892/ol.2017.6905. Epub 2017 Sep 6.
It is generally accepted that alternative splicing has an effect on disease when it leads to conspicuous changes in relevant proteins, but that the combinatorial effect of several small modifications can have marked outcomes as well. Inflammation is a complex process involving numerous signaling pathways, among which the tumor necrosis factor (TNF) pathway is one of the most studied. Signaling pathways are commonly represented as intricate cascades of molecular interactions that eventually lead to the activation of one or several genes. Alternative splicing is a common means of controlling protein expression in time and space; therefore, it can modulate the outcome of signaling pathways through small changes in their elements. Notably, the overall process is tightly regulated, which is easily overlooked when analyzing the pathway as a whole. The present review summarizes recent studies of the alternative splicing of key players of the TNF pathway leading to inflammation, and hypothesizes on the cumulative results of those modifications and the impact on cancer development.
人们普遍认为，当可变剪接导致相关蛋白质发生显著变化时，它会对疾病产生影响，但几个小修饰的组合效应也可能产生显著结果。炎症是一个涉及众多信号通路的复杂过程，其中肿瘤坏死因子（TNF）通路是研究最多的通路之一。信号通路通常表现为复杂的分子相互作用级联，最终导致一个或几个基因的激活。可变剪接是在时间和空间上控制蛋白质表达的常见方式；因此，它可以通过信号通路元件的微小变化来调节信号通路的结果。值得注意的是，整个过程受到严格调控，在整体分析该通路时很容易被忽视。本综述总结了导致炎症的TNF通路关键参与者可变剪接的最新研究，并对这些修饰的累积结果及其对癌症发展的影响进行了推测。
