Laboratory of Tumour and Development Biology, GIGA-Cancer Unit, Tour de Pathologie B23, University of Liège, 4000 - Liège, Belgium.
Curr Pharm Des. 2010;16(35):3864-76. doi: 10.2174/138161210794455012.
In eukaryotes, genes consist in coding sequences (exons) interspersed with non-coding ones (introns). The regulation of alternative inclusion/exclusion of exons, or part of exons, during the maturation of the pre-mRNA into mRNA (alternative splicing) allows a dramatic increase of the protein versus the gene repertoire. In a number of cases, alternative splicing decision generates proteins with distinct, sometimes opposite, functions from a given gene. Angiogenesis is the process of vascularisation in physiological conditions and a series of pathologies, including cancer where it favours tumour progression and dissemination of metastasis. In this issue, we discuss some key examples showing how alternative splicing may induce a switch from anti-angiogenic to pro-angiogenic functions and reciprocally. For some of these splicing events, the molecular mechanisms that trigger alternative splicing toward one or the other direction start to be elucidated. The emergence of strategies enabling to regulate alternative splicing opens new routes for anti-angiogenic therapies.
在真核生物中，基因由编码序列（外显子）和非编码序列（内含子）组成。在 pre-mRNA 成熟为 mRNA 的过程中，外显子或外显子的一部分的选择性包含/排除（可变剪接）允许蛋白质相对于基因库发生显著增加。在许多情况下，可变剪接决定产生具有不同功能的蛋白质，有时甚至是相反的功能，来自给定的基因。血管生成是生理条件下血管生成的过程，也是一系列病理学的过程，包括癌症，它有利于肿瘤的进展和转移的扩散。在本期中，我们讨论了一些关键的例子，展示了可变剪接如何诱导从抗血管生成到促血管生成功能的转变，反之亦然。对于其中的一些剪接事件，开始阐明触发向一个或另一个方向进行可变剪接的分子机制。能够调节可变剪接的策略的出现为抗血管生成治疗开辟了新的途径。
