Yoo Peter S, Mulkeen Abby L, Cha Charles H
World J Gastroenterol. 2006 Aug 21;12(31):4937-42. doi: 10.3748/wjg.v12.i31.4937.
Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.
血管内皮生长因子(VEGF)是一种强效的分泌型促有丝分裂原,对生理和肿瘤血管生成至关重要。VEGF的调控发生在多个层面,包括转录、mRNA稳定、翻译以及各种异构体的细胞定位差异。我们对VEGF转录后调控的理解最近取得的进展包括鉴定出稳定mRNA的结合蛋白HuR,以及在VEGF mRNA的5'非翻译区发现内部核糖体进入位点。单克隆抗VEGF抗体最近已被批准用于人体,但需要高全身剂量。RNA干扰(RNAi)技术正在体外和动物模型中使用,取得了有前景的结果。在这里,我们综述了关于VEGF转录后调控的文献,并描述了针对这些机制以获得治疗益处的最新进展。