Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, Canada.
Wiley Interdiscip Rev RNA. 2012 Jan-Feb;3(1):13-25. doi: 10.1002/wrna.101. Epub 2011 Jul 27.
Studies in the past several years highlight important features of the messenger RNA (mRNA) export process. For instance, groups of mRNAs acting in the same biochemical processes can be retained or exported in a coordinated manner thereby impacting on specific biochemistries and ultimately on cell physiology. mRNAs can be transported by either bulk export pathways involving NXF1/TAP or more specialized pathways involving chromosome region maintenance 1 (CRM1). Studies on primary tumor specimens indicate that many common and specialized mRNA export factors are dysregulated in cancer including CRM1, eukaryotic translation initiation factor 4E (eIF4E), HuR, nucleoporin 88, REF/Aly, and THO. This positions these pathways as potential therapeutic targets. Recently, specific targeting of the eIF4E-dependent mRNA export pathway in a phase II proof-of-principle trial with ribavirin led to impaired eIF4E-dependent mRNA export correlating with clinical responses including remissions in leukemia patients. Here, we provide an overview of these mRNA export pathways and highlight their relationship to cancer.
过去几年的研究强调了信使 RNA（mRNA）输出过程的重要特征。例如，在同一生化过程中起作用的mRNA 组可以以协调的方式被保留或输出，从而影响特定的生物化学过程，并最终影响细胞生理学。mRNA 可以通过涉及 NXF1/TAP 的批量输出途径或涉及染色体区域维持 1（CRM1）的更专门的途径进行运输。对原发性肿瘤标本的研究表明，包括 CRM1、真核翻译起始因子 4E（eIF4E）、HuR、核孔蛋白 88、REF/Aly 和 THO 在内的许多常见和专门的 mRNA 输出因子在癌症中失调。这使这些途径成为潜在的治疗靶点。最近，在一项使用利巴韦林的 II 期概念验证试验中，对 eIF4E 依赖性 mRNA 输出途径进行了特异性靶向，导致依赖于 eIF4E 的 mRNA 输出受损，与包括白血病患者缓解在内的临床反应相关。在这里，我们概述了这些 mRNA 输出途径，并强调了它们与癌症的关系。
